VMAT2 INHIBITORS AND METHODS OF USE BACKGROUND Technical Field This disclosure relates to, inter alia, certain compounds, compositions, and pharmaceutical compositions thereof, that modulate the activity of the transporter protein vesicular monoamine transporter-2 (VMAT2) and are directed to methods useful in the treatment of transporter protein vesicular monoamine transporter-2 mediated disorders, such as, neurological or psychiatric disease or disorders, including but not limited to, hyperkinetic movement disorders (e.g., tardive dyskinesia, Tourette's syndrome, Huntington's disease, tics, ataxia, chorea (such as, chorea associated with Huntington's disease), dystonia, hemifacial spasm, myoclonus, restless leg syndrome, and tremors). The disclosure further relates to synthetic methods and intermediates useful in the preparation of the compounds. Description of the Related Technology Dysregulation of dopaminergic systems is integral to several central nervous system (CNS) disorders, including neurological and psychiatric diseases and disorders. These neurological and psychiatric diseases and disorders include hyperkinetic movement disorders, and conditions, such as, schizophrenia and mood disorders. The transporter protein vesicular monoamine transporter-2 (VMAT2) plays an important role in presynaptic dopamine release and regulates monoamine uptake from the cytoplasm to the synaptic vesicle for storage and release. (±)-Tetrabenazine ((±)-TBZ), has been used as a drug for decades. (±)-TBZ is reported as a potent, reversible inhibitor of catecholamine uptake by VMAT2 (IC50 = 3.2 nM) (see, e.g., Scherman et al., Proc. Natl. Acad. Sci. USA, (1983) 80:584-8) and is currently used in the treatment of various hyperkinetic disorders. Inhibition of VMAT2 by (±)-TBZ results in depletion of brain monoamines in vivo (see, e.g., Pettibone et al., Eur. J. Pharmacol. (1984) 102:431-6). (±)-TBZ also inhibits presynaptic and postsynaptic dopamine receptors in rat brain (see, e.g., Login et al., (1982) Ann. Neurology 12:257-62; Reches et al., J. Pharmacol. Exp. Ther. (1983) 225:515-521). (±)-TBZ exhibits extensive first pass metabolism following oral administration to humans with little or no (±)-TBZ observed in systemic circulation. The pharmacological activity of (±)-TBZ is therefore thought to be mediated primarily by active metabolites. (±)-TBZ has two chiral centers and is a racemic mixture of two stereoisomers. (±)-TBZ has been determined to be rapidly and extensively metabolized in vivo by carbonyl reductase to four metabolic stereoisomers of 3-isobutyl-9,10-dimethoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, also known as dihydrotetrabenazine (DHTBZ). The inhibitory constants of these four metabolites for VMAT2 have been reported, such as, in WO2008/058261, Example 7. As shown, only two of the four DHTBZ isomers ([+]-alpha-DHTBZ and [+]-beta-DHTBZ) show significant potency as inhibitors of VMAT2. In patients administered (±)-TBZ, [-]-alpha-DHTBZ (2S,3S,11bS-DHTBZ) and [+]-beta- DHTBZ (2S,3R,11bR-DHTBZ) were the most abundant DHTBZ isomers, while [-]-beta-DHTBZ (2R,3S,11bS-DHTBZ) and [+]-alpha-DHTBZ (2R,3R,11bR-DHTBZ) were present as minor metabolites. The [+]-alpha-DHTBZ (2R,3R,11bR-DHTBZ) isomer was determined to be present in the least amount of all four isomers. Thus, [+]-beta-DHTBZ (2S,3R,11bR-DHTBZ) appears to be the major DHTBZ isomer contributing to the pharmacological activity of (±)-TBZ. Once formed, the half-life of [+]-beta-DHTBZ (2S,3R,11bR-DHTBZ) is relatively short (approximately 5 hours) which requires (±)-TBZ to have a sub-optimal (TID) dosing regimen. (±)-TBZ has a narrow therapeutic window, and its clinical use requires careful dose titration. Side effects associated with (±)-TBZ and/or its metabolites include neuroleptic malignant syndrome, drowsiness, fatigue, nervousness, anxiety, insomnia, agitation, confusion, orthostatic hypotension, nausea, dizziness, sedation, depression, akathisia, and Parkinsonism. Generally speaking, the probability of observing side effects is a function of the achieved plasma concentrations from a given dosing regimen. Compounds with a longer half-life (t _1/2 ) and lower clearance will have lower peak-to- trough fluctuations in plasma exposure given an equivalent dosing interval. These longer half-life compounds may exhibit improved tolerability by maintaining drug concentrations at levels needed for efficacy but below levels that may elicit side effects. A fundamental and effective strategy to improve drug half-life is to reduce clearance. The term clearance describes the process of drug elimination from the body or from a single organ, defined as the volume of fluid cleared of drug from the body per unit of time. Clearance is a fundamental pharmacokinetic parameter and is commonly measured in drug research and development as this parameter impacts drug attributes such as half-life and, ultimately, the dosing regimen. When compound and dose selection is optimized, the benefits of small plasma-concentration fluctuations seen in compounds with low clearance include potentially reduced steady state peak concentrations, increased trough concentrations, and the prospect of improving medication adherence because of a possibly improved risk-benefit profile. Despite the advances that have been made in this field, a need remains in the art for improved VMAT2 inhibitors, including compounds, compositions, and methods related thereto. The identification of long half-life / low clearance VMAT2 small molecule inhibitors is advantageous for drug development, particularly when being developed for chronic administration. In certain disease populations where patient compliance and pill burden are an ongoing challenge, reduced dosing frequency is highly desirable and offers increased patient benefit. The present disclosure fulfills these, such as, improved in vitro VMAT2 potency or improved pharmacokinetics, or both, and other needs, as evident in reference to the following disclosure. SUMMARY One aspect of the present disclosure encompasses, inter alia, a compound of Formula (Ia): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ is selected from: C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene, C ₁ -C ₆ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₁ -C ₄ - alkyl-O-C ₂ -C ₄ -alkylene, C ₃ -C ₇ -cycloalkyl-O-C ₂ -C ₄ -alkylene, 3-7-membered-heterocyclyl, 3-7- membered-heterocyclyl-C ₁ -C ₄ -alkylene, C ₄ -C ₈ -bicycloalkyl-C ₁ -C ₄ -alkylene, C ₄ -C ₇ -cycloalkenyl, 5- 11-membered-spiro-heterocyclyl, C ₅ -C ₁₁ -spiro-cycloalkyl, cubanyl-C ₁ -C ₄ -alkylene, and 4-8- membered-heterobicyclyl-C ₁ -C ₄ -alkylene; wherein each R ¹ group is optionally substituted with one or more substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, cyano, C ₁ -C ₄ -alkylsulfonyl, C ₃ -C ₆ - cycloalkyl, hydroxyl, C ₁ -C ₄ -alkoxy, and C ₂ -C ₄ -dialkylamino. Also provided herein are pharmaceutical products selected from: a pharmaceutical composition, a formulation, a unit dosage form, and a kit; each comprising a compound, as described herein, or a pharmaceutically acceptable salt thereof. Also provided herein are pharmaceutical products selected from: a pharmaceutical composition, a formulation, a unit dosage form, and a kit; each comprising a compound, as described herein, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. Also provided herein are pharmaceutical compositions comprising a compound, as described herein, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. Also provided herein are methods for preparing a pharmaceutical composition comprising the step of admixing a compound, as described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Also provided herein are methods of treating a vesicular monoamine transporter-2 (VMAT2) disease or disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein. Also provided herein are methods of treating a vesicular monoamine transporter-2 (VMAT2) disease or disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; wherein the VMAT2 disease or disorder is selected from: an ataxias or spinal muscular atrophy; a chorea; a congenital malformation, deformation, or abnormality; a dementia; an oral cavity, salivary gland, or jaw disease; a dyskinesia; a dystonia; an endocrine, nutritional, or metabolic disease; an epilepsy; a habit or impulse disorder; a Huntington’s disease or related disorder; a mood or psychotic disorder; a neurotic, stress-related, and somatoform disorder; a degenerative disease of the basal ganglia; an extrapyramidal and movement disorder; a neurological or psychiatric disease or disorder; a nervous system or motor function disorder; a Parkinson’s/parkinsonism disorder; a pediatric-onset behavioral and emotional disorder; a pervasive developmental disorder; and a substance abuse or dependence disorder. Also provided herein are methods of treating a neurological or psychiatric disease or disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein. Also provided herein are methods of treating a neurological or psychiatric disease or disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; wherein the neurological or psychiatric disease or disorder is selected from the group consisting of: hyperkinetic movement disorder, schizophrenia, schizoaffective disorder, a mood disorder, treatment-refractory obsessive-compulsive disorder, neurological dysfunction associated with Lesch-Nyhan syndrome, agitation associated with Alzheimer’s disease, Fragile X syndrome or Fragile X-associated tremor-ataxia syndrome, autism spectrum disorder, Rett syndrome, and chorea-acanthocytosis. Also provided herein are methods of treating a neurological or psychiatric disease or disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; wherein the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder. Also provided herein are methods of treating a hyperkinetic movement disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; wherein the hyperkinetic movement disorder is selected from the group consisting of: tardive dyskinesia, Tourette's syndrome, Huntington's disease, tics, chorea associated with Huntington's disease, ataxia, chorea, dystonia, hemifacial spasm, myoclonus, restless leg syndrome, and tremors. Also provided herein are methods of treating a hyperkinetic movement disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; wherein the hyperkinetic movement disorder is tardive dyskinesia. Also provided herein are methods of treating a hyperkinetic movement disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; wherein the hyperkinetic movement disorder is Huntington's disease. Also provided herein are methods of treating a hyperkinetic movement disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; wherein the hyperkinetic movement disorder is chorea associated with Huntington's disease. Also provided herein are methods of treating a neurological or psychiatric disease or disorder in a subject in need thereof, comprising administering to the subject a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; wherein the neurological or psychiatric disease or disorder is selected from schizophrenia and schizoaffective disorder. In some embodiments, the neurological or psychiatric disease or disorder is schizophrenia. In some embodiments, the neurological or psychiatric disease or disorder is schizoaffective disorder. In some embodiments, the neurological or psychiatric disease or disorder is obsessive-compulsive disorder. In some embodiments, the neurological or psychiatric disease or disorder is treatment-refractory obsessive- compulsive disorder. In some embodiments, the neurological or psychiatric disease or disorder is autism spectrum disorder. In some embodiments, the method comprises using the compound, salt, product, or composition in adjunctive therapy. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating a vesicular monoamine transporter-2 (VMAT2) disease or disorder. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating a vesicular monoamine transporter-2 (VMAT2) disease or disorder selected from: an ataxias or spinal muscular atrophy; a chorea; a congenital malformation, deformation, or abnormality; a dementia; an oral cavity, salivary gland, or jaw disease; a dyskinesia; a dystonia; an endocrine, nutritional, or metabolic disease; an epilepsy; a habit or impulse disorder; a Huntington’s disease or related disorder; a mood or psychotic disorder; a neurotic, stress-related, and somatoform disorder; a degenerative disease of the basal ganglia; an extrapyramidal and movement disorder; a neurological or psychiatric disease or disorder; a nervous system or motor function disorder; a Parkinson’s/parkinsonism disorder; a pediatric-onset behavioral and emotional disorder; a pervasive developmental disorder; and a substance abuse or dependence disorder. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating a neurological or psychiatric disease or disorder. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating a neurological or psychiatric disease or disorder selected from the group consisting of: hyperkinetic movement disorder, schizophrenia, schizoaffective disorder, a mood disorder, treatment-refractory obsessive-compulsive disorder, neurological dysfunction associated with Lesch-Nyhan syndrome, agitation associated with Alzheimer’s disease, Fragile X syndrome or Fragile X-associated tremor-ataxia syndrome, autism spectrum disorder, Rett syndrome, and chorea-acanthocytosis. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating a hyperkinetic movement disorder. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating a hyperkinetic movement disorder; wherein the hyperkinetic movement disorder is selected from the group consisting of: tardive dyskinesia, Tourette's syndrome, Huntington's disease, tics, chorea associated with Huntington's disease, ataxia, chorea, dystonia, hemifacial spasm, myoclonus, restless leg syndrome, and tremors. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating tardive dyskinesia. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating Huntington's disease. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating chorea associated with Huntington's disease. Also provided herein are uses of a compound, as described herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical product as described herein; or a pharmaceutical composition as described herein; in the manufacture of a medicament for treating a neurological or psychiatric disease or disorder, wherein the neurological or psychiatric disease or disorder is selected from schizophrenia and schizoaffective disorder. In some embodiments, the neurological or psychiatric disease or disorder is schizophrenia. In some embodiments, the neurological or psychiatric disease or disorder is schizoaffective disorder. In some embodiments, the neurological or psychiatric disease or disorder is obsessive-compulsive disorder. In some embodiments, the neurological or psychiatric disease or disorder is treatment-refractory obsessive-compulsive disorder. In some embodiments, the neurological or psychiatric disease or disorder is autism spectrum disorder. In some embodiments, treatment comprises using the compound, salt, product, or composition in adjunctive therapy. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method of treatment of the human or animal body by therapy. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating a vesicular monoamine transporter-2 (VMAT2) disease or disorder. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating a vesicular monoamine transporter-2 (VMAT2) disease or disorder selected from: an ataxias or spinal muscular atrophy; a chorea; a congenital malformation, deformation, or abnormality; a dementia; an oral cavity, salivary gland, or jaw disease; a dyskinesia; a dystonia; an endocrine, nutritional, or metabolic disease; an epilepsy; a habit or impulse disorder; a Huntington’s disease or related disorder; a mood or psychotic disorder; a neurotic, stress-related, and somatoform disorder; a degenerative disease of the basal ganglia; an extrapyramidal and movement disorder; a neurological or psychiatric disease or disorder; a nervous system or motor function disorder; a Parkinson’s/parkinsonism disorder; a pediatric-onset behavioral and emotional disorder; a pervasive developmental disorder; and a substance abuse or dependence disorder. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating a neurological or psychiatric disease or disorder. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating a neurological or psychiatric disease or disorder selected from the group consisting of: hyperkinetic movement disorder, schizophrenia, schizoaffective disorder, a mood disorder, treatment-refractory obsessive-compulsive disorder, neurological dysfunction associated with Lesch-Nyhan syndrome, agitation associated with Alzheimer’s disease, Fragile X syndrome or Fragile X-associated tremor-ataxia syndrome, autism spectrum disorder, Rett syndrome, and chorea-acanthocytosis. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating a hyperkinetic movement disorder. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating a hyperkinetic movement disorder; wherein the hyperkinetic movement disorder is selected from the group consisting of: tardive dyskinesia, Tourette's syndrome, Huntington's disease, tics, chorea associated with Huntington's disease, ataxia, chorea, dystonia, hemifacial spasm, myoclonus, restless leg syndrome, and tremors. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating tardive dyskinesia. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating Huntington's disease. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating chorea associated with Huntington's disease. Also provided herein are compounds, as described herein, or a pharmaceutically acceptable salt thereof, for use in a method for treating a neurological or psychiatric disease or disorder, wherein the neurological or psychiatric disease or disorder is selected from schizophrenia and schizoaffective disorder. In some embodiments, the neurological or psychiatric disease or disorder is schizophrenia. In some embodiments, the neurological or psychiatric disease or disorder is schizoaffective disorder. In some embodiments, the neurological or psychiatric disease or disorder is obsessive-compulsive disorder. In some embodiments, the neurological or psychiatric disease or disorder is treatment- refractory obsessive-compulsive disorder. In some embodiments, the neurological or psychiatric disease or disorder is autism spectrum disorder. In some embodiments, the method for treating comprises using the compound, salt, product, or composition in adjunctive therapy. These and other aspects of the invention disclosed herein will be set forth in greater detail as the patent disclosure proceeds. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1A shows a general synthetic scheme for the preparation of certain compounds of Formula (Ia) and intermediates related thereto, wherein R ¹ is methyl. In this representative example, R ¹ is methyl and is introduced in Compound 2-3. FIG.1B shows a general synthetic scheme for the preparation of certain compounds of Formula (Ia) and an intermediate related thereto, wherein R ¹ is methyl. In this representative example, compounds (i.e., Compound 15, Compound 76, Compound 77, and Compounds 78) were isolated by supercritical fluid chromatography (SFC) as described in Example 1. FIG.2A shows a general synthetic scheme for the preparation of (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]i soquinoline-2,9-diol (Compound 2- 22) utilizing intermediate (±)-1-(6-(benzyloxy)-7-methoxy-1,2,3,4-tetrahydroisoquinoli n-1-yl)-3-(tert- butoxy)propan-2-one (Compound 2-17) and a resolution step of (±)-9-(benzyloxy)-3-(tert-butoxy)- 10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinol in-2-ol (Compound (±)-2-19) with (2S,3S)-2,3-bis(4-methylbenzoyloxy)butanedioic acid (DPTTA) to provide (2R,3R,11bR)-9- (benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 2-21) that is subsequently deprotected to provide Compound 2-22. FIG.2B shows a general synthetic scheme for the preparation of (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]i soquinoline-2,9-diol (Compound 2- 22) utilizing intermediates 1-(tert-butoxy)propan-2-one (Compound 2-25) and 3-(tert-butoxy)-4- (dimethylamino)butan-2-one (Compound 2-26) to give (±)-9-(benzyloxy)-3-(tert-butoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-one (Compound (±)-2-18) that is subsequently reduced to provide (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-19). A resolution step of Compound (±)-2-19 with (2S,3S)-2,3-bis(4-methylbenzoyloxy)butanedioic acid (DPTTA) is utilized to provide (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4, 6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 2-21) that is subsequently deprotected to provide Compound 2-22. FIG.3 shows a general synthetic scheme for the preparation of compounds of Formula (Ia) utilizing 3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1-a]isoquinoline-2,9-diol, and different alkylating agents; wherein R ¹ has the same meaning as described herein, LG ¹ is a Leaving Group, and R ^3a can be H or C1-C4-alkyl optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-haloalkyl, cyano, C1-C4-alkylsulfonyl, C3-C6- cycloalkyl, C1-C4-alkoxy, and C2-C4-dialkylamino. It is understood that LG ¹ can be a variety of leaving groups, such as those described herein and those known in the art. FIG.4 shows a general synthetic scheme for the preparation of compounds of Formula (Ie) utilizing (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1- a]isoquinoline-2,9-diol (Compound 2-22), and different alkylating agents; wherein R ¹ has the same meaning as described herein, LG ¹ is a Leaving Group, and R ^3a can be H or C ₁ -C ₄ -alkyl optionally substituted with one or more substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, C ₁ -C ₄ - haloalkyl, cyano, C1-C4-alkylsulfonyl, C3-C6-cycloalkyl, C1-C4-alkoxy, and C2-C4-dialkylamino. It is understood that LG ¹ can be a variety of leaving groups, such as those described herein and those known in the art. FIG.5 shows in vivo pharmacology in Sprague Dawley rats for (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-(3,3,3-trifluoropropoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol Compound 18 and (2R,3R,11bR)-3-(tert-butoxy)-9-ethoxy-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol Compound 22 in the Open Field Hypolocomotion model as described in Example 15. DETAILED DESCRIPTION DEFINITIONS For clarity and consistency, the following definitions will be used throughout this patent document. As used herein, “about” means ± 20% of the stated value, and includes more specifically values of ± 10%, ± 5%, ± 2%, and ± 1% of the stated value. The terms “adjunctive treatment”, “adjunctive therapy”, “co-therapy”, “combination therapy”, and “combined treatment” as used herein refers to the treatment of a patient in need thereof by administering a compound (as described herein) in combination with one or more medications, wherein the administration is by any suitable means, such as, simultaneously, sequentially, separately, or in a single pharmaceutical formulation. The terms “administering” and “administration” as used herein refer to providing a compound described herein or other therapy to a subject in a form that can be introduced into that subject’s body in a therapeutically useful form and therapeutically useful amount, including, but not limited to: oral dosage forms, such as, tablets, capsules, syrups, suspensions, and the like; injectable dosage forms, such as, intravenous (IV), intramuscular (IM), subcutaneous (SC), and the like; transdermal dosage forms, including creams, jellies, powders, and patches; buccal dosage forms; inhalation powders, sprays, suspensions, and the like; and rectal dosages forms, such as, suppositories. A health care practitioner can directly provide a compound described herein to a subject in the form of a sample or can indirectly provide a compound to a subject by providing an oral or written prescription for the compound. Also, for example, a subject can obtain a compound by themselves without the involvement of a health care practitioner. When the compound is administered to the subject, the body is transformed by the compound in some way. When a compound, as described herein, is provided in combination with one or more other agents, “administering” and “administration” are understood to include the compound and at least one other agent are administered at the same time or at different times. When the agents of a combination are administered at the same time, they can be administered together in a single composition, or they can be administered separately. The preferred method of administration can vary depending on various factors, e.g., the components of the pharmaceutical formulation, the site of the disease, and the severity of the disease. The term “composition” refers to a compound or crystalline form thereof, including but not limited to, salts, solvates, and hydrates of a compound described herein, in combination with at least one additional component, such as, a composition obtained/prepared during synthesis, preformulation, in-process testing (e.g., TLC, HPLC, NMR samples), and the like. The term, “compound” as used herein refers to all stereoisomers, geometric isomers, tautomers, and isotopic variants of the structures depicted herein. The term is also meant to refer to compounds described herein, regardless of how they are prepared, e.g., synthetically, through biological process (e.g., metabolism or enzyme conversion), or a combination thereof. All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances, such as, water and solvents (e.g., hydrates and solvates) or can be isolated. When in the solid state, the compounds described herein and salts thereof can occur in various forms and can, e.g., take the form of co-crystals or solvates, including hydrates. The compounds can be in any solid-state form, such as, a polymorph or solvate, so unless clearly indicated otherwise, reference in the specification to compounds and salts thereof should be understood as encompassing any solid-state form of the compound. In some embodiments, the compounds described herein, or salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, e.g., a composition enriched in the compounds described herein. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compounds described herein, or salts thereof. The term “solvate” as used herein refers to a compound, as described herein, or a pharmaceutically acceptable salt thereof, which includes a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. When the solvent is water, the solvate is a hydrate. The term “hydrate” as used herein refers to a compound, as described herein, or a pharmaceutically acceptable salt thereof, that further includes a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces. The term “in need of treatment” and the term “in need thereof” when referring to treatment are used interchangeably to mean a judgment made by a caregiver (e.g., physician, nurse, nurse practitioner, etc. in the case of humans; veterinarian in the case of animals, including non-human mammals) that a subject or animal requires or will benefit from treatment. This judgment is made based on a variety of factors that are in the realm of a caregiver's expertise, but that includes the knowledge that the subject or animal is ill, or will become ill, as the result of a disease, condition or disorder that is treatable by the compound described herein. Accordingly, the compound described herein can be used in a protective or preventive manner; or compound described herein can be used to alleviate, inhibit, or ameliorate the disease, condition, or disorder. The term “subject” refers to any animal, including mammals, such as, mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, primates, and humans. In the context of a clinical trial or screening or activity experiment the subject can be a healthy volunteer or healthy participant without an underlying VMAT2 mediated disorder or condition or a volunteer or participant that has received a diagnosis for a disorder or condition in need of medical treatment as determined by a health care professional. In the context outside of a clinical trial a subject under the care of a health care professional who has received a diagnosis for a disorder or condition is typically described as a subject. The term “pediatric subject” refers to a subject under the age of 21 years at the time of diagnosis or treatment. The term “pediatric” can be further divided into various subpopulations including: neonates (from birth through the first month of life); infants (1 month up to two years of age); children (two years of age up to 12 years of age); and adolescents (12 years of age through 21 years of age (up to, but not including, the twenty-second birthday)) see e.g., Berhman et al., Textbook of Pediatrics, 15th Ed. Philadelphia: W.B. Saunders Company, 1996; Rudolph et al., Rudolph’s Pediatrics, 21st Ed. New York: McGraw-Hill, 2002; and Avery et al., Pediatric Medicine, 2nd Ed. Baltimore: Williams & Wilkins; 1994. The phrase “pharmaceutically acceptable” refers to compounds (and salts thereof), compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. The term “pharmaceutical composition” refers to a specific composition comprising at least one active ingredient; including but not limited to, salts, solvates, and hydrates of compounds described herein, whereby the composition is amenable to investigation for a specified, efficacious outcome in a mammal (for example, without limitation, a human). Those of ordinary skill in the art will understand and appreciate the techniques appropriate for determining whether an active ingredient has a desired efficacious outcome based upon the needs of the artisan. The terms “prevent”, “preventing”, and “prevention” refer to the elimination or reduction of the occurrence or onset of one or more symptoms associated with a particular disorder. For example, the terms “prevent”, “preventing”, and “prevention” can refer to the administration of therapy on a prophylactic or preventative basis to a subject who may ultimately manifest at least one symptom of a disorder but who has not yet done so. Such subjects can be identified on the basis of risk factors that are known to correlate with the subsequent occurrence of the disease, such as, the presence of a biomarker. Alternatively, prevention therapy can be administered as a prophylactic measure without prior identification of a risk factor. Delaying the onset of the at least one episode and/or symptom of a disorder can also be considered prevention or prophylaxis. In some embodiments, the subject can be a pediatric subject. The terms “treat”, “treating”, and “treatment” refer to medical management of a disease, disorder, or condition of a subject (e.g., subject) (see, e.g., Stedman’s Medical Dictionary). In general, an appropriate dose and treatment regimen provide the VMAT2 inhibitor in an amount sufficient to provide therapeutic benefit. Therapeutic benefit for subjects to whom the VMAT2 inhibitor compound(s) described herein are administered, includes, for example, an improved clinical outcome, wherein the object is to prevent or slow or retard (lessen) an undesired physiological change associated with the disease, or to prevent or slow or retard (lessen) the expansion or severity of such disease. The effectiveness of one or more VMAT2 inhibitors can include beneficial or desired clinical results that comprise, but are not limited to, abatement, lessening, or alleviation of symptoms that result from or are associated with the disease to be treated; decreased occurrence of symptoms; improved quality of life; longer disease-free status (i.e., decreasing the likelihood or the propensity that a subject will present symptoms on the basis of which a diagnosis of a disease is made); diminishment of extent of disease; stabilized (i.e., not worsening) state of disease; delay or slowing of disease progression; amelioration or palliation of the disease state; and remission (whether partial or total), whether detectable or undetectable; and/or overall survival. In some embodiments, the subject can be a pediatric subject. The term “therapeutically effective amount” refers to the amount of the compound described herein, or a pharmaceutically acceptable salt thereof, or an amount of a pharmaceutical composition comprising the compound described herein or a pharmaceutically acceptable salt thereof, that elicits the biological or medicinal response in a tissue, system, animal, or human that is being sought by a subject, researcher, veterinarian, medical doctor, or other clinician or caregiver, which can include one or more of the following: (1) preventing the disorder, for example, preventing a disease, condition, or disorder in a subject who can be predisposed to the disease, condition, or disorder but does not yet experience or display the relevant pathology or symptomatology; (2) inhibiting the disorder, for example, inhibiting a disease, condition, or disorder in a subject who is experiencing or displaying the relevant pathology or symptomatology (i.e., arresting further development of the pathology and/or symptomatology); and (3) ameliorating the disorder, for example, ameliorating a disease, condition, or disorder in a subject who is experiencing or displaying the relevant pathology or symptomatology (i.e., reversing the pathology and/or symptomatology). The term “contacting” refers to the bringing together of indicated moieties in an in vitro system or an in vivo system. For example, “contacting” the VMAT2 protein with a compound provided herein includes the administration of a compound provided herein (or a pharmaceutically acceptable salt thereof) to a subject, such as, a human, having a VMAT2 protein, as well as, for example, introducing a compound provided herein into a sample containing a cellular or purified preparation containing the VMAT2 protein. CHEMICAL GROUPS Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents, applications, published applications, and other publications are incorporated by reference in their entirety. In the event that there is a plurality of definitions for a term herein, those in this section prevail unless stated otherwise. The term “a-membered” (wherein “a” is an integer) preceding the name of a group refers to the number of atoms in that group. For example, oxetanyl contains four atoms and is a 4-membered- heterocyclyl; 2-oxaspiro[3.3]heptanyl is an example of a 7-membered-spiro-heterocyclyl; and piperidinyl is an example of a 6-membered-heterocyclyl ring. Similarly, the term “a-b-membered” (wherein “a” and “b” are integers) preceding the name of a group refers to the inclusive range of atoms in that group. For example, a “3-7-membered-heterocyclyl” group refers to all “heterocyclyl” groups having from 3 to 7 atoms (i.e., 3, 4, 5, 6, and 7 atoms), where “heterocyclyl” is defined herein; and “4-5-membered-heterocyclyl” refers to all “heterocyclyl” groups having from 4 to 5 atoms (i.e., 4 and 5 atoms). If no “a” and “b” are designated with regard to a group, the broadest range described in these definitions is to be assumed. For compounds, as described herein, or pharmaceutically acceptable salts thereof, in which a variable appears more than once, each variable can be a different moiety independently selected from the group defining the variable. For example, where a structure is described having, for example, two R groups that are simultaneously present on the same compound, the two R groups can represent different moieties independently selected from the group defined for R, or the two R groups can be the same. Whenever a group is described as being “substituted” that group can be substituted with one or more of the indicated substituents. Likewise, when a group is described as being “unsubstituted or substituted” if substituted, the substituent(s) can be selected from one or more of the indicated substituents. It is to be understood that substitution at a given atom is limited by valency. Further, it is understood that “optionally substituted” refers to the group as being unsubstituted or substituted. The term “Ca-Cb” (wherein “a” and “b” are integers) preceding the name of a group refers to the inclusive range of carbon atoms in that group. For example, a “C1-C4-alkyl” group refers to all alkyl groups having from 1 to 4 carbons (i.e., 1, 2, 3, and 4 carbons), such as, methyl (CH3-), ethyl (CH ₃ CH ₂ -), n-propyl (CH ₃ CH ₂ CH ₂ -), iso-propyl ((CH ₃ ) ₂ CH-), n-butyl (CH ₃ CH ₂ CH ₂ CH ₂ -), iso-butyl ((CH ₃ ) ₂ CHCH ₂ -), sec-butyl (CH ₃ CH ₂ CH(CH ₃ )-), and tert-butyl ((CH ₃ ) ₃ C-). If no “a” and “b” are designated with regard to a group, the broadest range described in these definitions is to be assumed. In addition to the foregoing, as used in the specification and claims, unless specified to the contrary, the following terms have the meaning indicated. The terms “C ₁ -C ₄ -alkylene” and “C ₂ -C ₄ -alkylene” refers to a straight or branched, saturated aliphatic, divalent radical having the defined number of carbons, 1 to 4 carbon atoms or 2 to 4 carbon atoms respectively. Some embodiments contain 1 to 2 carbons. Some embodiments contain 1 to 3 carbons. Some embodiments contain 1 carbon atom. Some embodiments contain 2 to 3 carbons. Some embodiments contain 2 carbon atoms. Examples include, but are not limited to, methylene (i.e., -CH ₂ - ), ethylene (i.e., -CH ₂ CH ₂ - and -CH(CH ₃ )-), n-propylene, isopropylene, n-butylene, s-butylene, isobutylene, and t-butylene. When one or more substituents are present on the “alkylene” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “alkylene” group can be substituted or unsubstituted. The term “C1-C4-alkyl-O-C2-C4-alkylene” refers to a radical group consisting of a “C1-C4- alkyl” group bonded to an oxygen atom and the oxygen atom is bonded to a “C2-C4 alkylene” radical, wherein “C1-C4-alkyl” and “C2-C4 alkylene” have the same definitions as described herein. Examples include, but are not limited to, 1-methoxyethyl (i.e., CH3-O-CH(CH3)-), 2-methoxyethyl (i.e., CH3-O-CH2CH2-), 2-ethoxyethyl, 2-propoxyethyl, 2-isopropoxyethyl, 3-methoxypropyl, 3- ethoxypropyl, 3-propoxypropyl, and 3-isopropoxypropyl. In some embodiments, “C1-C4-alkyl-O-C2- C4-alkylene” refers to a group selected from: 2-methoxyethyl (i.e., CH3-O-CH2CH2-), 2-ethoxyethyl, 2-propoxyethyl, 2-isopropoxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 3-propoxypropyl, and 3- isopropoxypropyl. When one or more substituents are present on the “C1-C4-alkyl-O-C2-C4- alkylene” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “C1-C4- alkyl-O-C2-C4-alkylene” group can be substituted or unsubstituted. The term “alkoxy” refers to a radical comprising an “alkyl” group attached directly to an oxygen atom, wherein “alkyl” has the same definition as found herein. Some embodiments contain 1 to 4 carbons (i.e., “C1-C4-alkoxy”). Some embodiments contain 1 to 3 carbons (i.e., “C1-C3-alkoxy”). Some embodiments contain 1 or 2 carbons. Examples include, but are not limited to, methoxy, ethoxy, n-propoxy, 1-methylethoxy (iso-propoxy), n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy. The term “alkyl” refers to a fully saturated straight or branched hydrocarbon radical. In some embodiments, the alkyl group can have 1 to 6 carbons (i.e., “C1-C6-alkyl”). Some embodiments are 1 to 5 carbons (i.e., “C1-C5-alkyl”), some embodiments are 1 to 4 carbons (i.e., C1-C4-alkyl), some embodiments are 1 to 3 carbons (i.e., “C1-C3-alkyl”), and some embodiments are 1 or 2 carbons. By way of example only, “C1-C4-alkyl” indicates that there are one to four carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec- butyl, and tert-butyl. Examples include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n- butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, iso-pentyl, tert-pentyl, neo-pentyl, 1-methylbutyl [i.e., -CH(CH ₃ )CH ₂ CH ₂ CH ₃ ], 2-methylbutyl [i.e., -CH ₂ CH(CH ₃ )CH ₂ CH ₃ ], and n-hexyl. When one or more substituents are present on the “alkyl” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “alkyl” group can be substituted or unsubstituted. The term “alkylsulfonyl” refers to a radical consisting of an “alkyl” radical bonded to the sulfur of a sulfone radical of the formula: -S(=O) ₂ -, wherein “alkyl” has the same definition as described herein. The “alkylsulfonyl” group can have 1 to 4 carbon atoms (i.e., “C ₁ -C ₄ - alkylsulfonyl”). Examples include, but are not limited to, methylsulfonyl, ethylsulfonyl, n- propylsulfonyl, iso-propylsulfonyl, n-butylsulfonyl, sec-butylsulfonyl, iso-butylsulfonyl, and t- butylsulfonyl. The term “amino” refers to the group -NH ₂ . The term “bicycloalkyl” refers to a radical comprising two fused or bridged cycloalkyl rings. In some embodiments, the “bicycloalkyl” group contains 4 to 8 ring carbon atoms. In some embodiments, the “bicycloalkyl” group contains 5 to 8 ring carbon atoms. In some embodiments, the “bicycloalkyl” group contains 5 to 7 ring carbon atoms. In some embodiments, the “bicycloalkyl” group contains 5 or 6 ring carbon atoms. Examples include, but are not limited to, bicyclo[1.1.0]butanyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.3.1]heptyl, and bicyclo[3.2.1]octyl. When one or more substituents are present on the “bicycloalkyl” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “bicycloalkyl” group can be substituted or unsubstituted. The term “C4-C8-bicycloalkyl-C1-C4-alkylene” refers to a radical group consisting of a “C4- C8-bicycloalkyl” group bonded to a “C1-C4 alkylene” radical, wherein “C4-C8-bicycloalkyl” and “C1-C4 alkylene” have the same definitions as described herein. Examples include, but are not limited to, (bicyclo[1.1.0]butan-1-yl)methyl (i.e., (bicyclo[1.1.0]butan-1-yl)CH2-), (bicyclo[1.1.1]pentan-1- yl)methyl (i.e., (bicyclo[1.1.1]pentan-1-yl)CH2-), (bicyclo[2.2.1]hex-1-yl)methyl, (bicyclo[2.2.1]hept- 1-yl)methyl, and (bicyclo[2.2.2]oct-1-yl)methyl. When one or more substituents are present on the “C4-C8-bicycloalkyl-C1-C4-alkylene” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “C4-C8-bicycloalkyl-C1-C4-alkylene” group can be substituted or unsubstituted. The term “4-8-membered-heterobicyclyl” refers to a radical comprising two fused or bridged rings comprising carbon atoms and at least one heteroatom. The heteroatom(s) include, but are not limited to, oxygen, sulfur, and nitrogen, when more than one heteroatom is present in the ring the heteroatoms can be the same or different. In some embodiments, the “4-8-membered- heterobicyclyl” is a group selected from: 2-oxabicyclo[2.1.1]hexan-1-yl and 2- oxabicyclo[2.1.1]hexan-4-yl. When one or more substituents are present on the “4-8-membered- heterobicyclyl” group, the substituent(s) can be bonded at any available ring atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “4- 8-membered-heterobicyclyl” group can be substituted or unsubstituted. The term “carbonyl” refers to the group -C(=O)-. The term “cubanyl” refers to a radical group with the following structure: . The term “cubanyl-C1-C4-alkylene” refers to a radical group consisting of a “cubanyl” group bonded to a “C1-C4 alkylene” radical, wherein “cubanyl” and “C1-C4 alkylene” have the same definitions as described herein. An example includes, but is not limited to, (cubanyl)methyl. When one or more substituents are present on the “cubanyl-C1-C4-alkylene” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “cubanyl-C1-C4-alkylene” group can be substituted or unsubstituted. The term “cyano” refers to the group -CN. The term “cyano-C1-C4-alkylene” refers to a radical group consisting of a “cyano” group bonded to a “C1-C4 alkylene” radical, wherein “cyano” and “C1-C4 alkylene” have the same definitions as described herein. Examples include, but are not limited to, cyanomethyl (i.e., -CH2CN), 2-cyanoethyl, 1-cyanoethyl (i.e., -CH(CH3)-CN), and 3-cyanopropyl. The term “cycloalkenyl” refers to a nonaromatic monocyclic hydrocarbon ring system containing at least one double bond in the ring. A “cycloalkenyl” group can contain 4 to 7 atoms in the ring (i.e., “C4-C7-cycloalkenyl”. Examples include, but are not limited to, cyclobutenyl, cyclopentenyl, cyclohexenyl, and cycloheptenyl. In some embodiments, “cycloalkenyl” is selected from: cyclobut-1-en-1-yl, cyclobut-2-en-1-yl, cyclopent-1-en-1-yl, cyclopent-2-en-1-yl, and cyclopent-3-en-1-yl. When one or more substituents are present on the “cycloalkenyl” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “cycloalkenyl” group can be substituted or unsubstituted. The term “cycloalkyl” refers to a fully saturated, all carbon, monocyclic ring system. In some embodiments, the cycloalkyl is a monocyclic ring containing 3 to 7 carbon atoms (i.e., “C3-C7- cycloalkyl”). Some embodiments contain 3 to 6 carbons (i.e., “C3-C6-cycloalkyl”). Some embodiments contain 3 to 5 carbons. Some embodiments contain 5 to 7 carbons. Some embodiments contain 3 to 4 carbons. Examples include, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. When one or more substituents are present on the “cycloalkyl” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “cycloalkyl” group can be substituted or unsubstituted. The term “C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene” refers to a radical group consisting of a “C ₃ - C ₇ -cycloalkyl” group bonded to a “C ₁ -C ₄ alkylene” radical, wherein “C ₃ -C ₇ -cycloalkyl” and “C ₁ -C ₄ alkylene” have the same definitions as described herein. Examples include, but are not limited to, cyclopropylmethyl (cyclopropyl-CH ₂ -), cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-cyclopropylethyl (cyclopropyl-CH ₂ CH ₂ -), 2-cyclobutylethyl, 2- cyclopentylethyl, 2-cyclohexylethyl, 2-cycloheptylethyl, 1-cyclopropylethyl (cyclopropyl-CH(CH ₃ )-), 1-cyclobutylethyl, 1-cyclopentylethyl, 1-cyclohexylethyl, 1-cycloheptylethyl, 3-cyclopropylpropyl, 3- cyclobutylpropyl, 3-cyclopentylpropyl, 3-cyclohexylpropyl, 3-cycloheptylpropyl, 4-cyclopropylbutyl, 4-cyclobutylbutyl, 4-cyclopentylbutyl, 4-cyclohexylbutyl, and 4-cycloheptylbutyl. When one or more substituents are present on the “C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene” group can be substituted or unsubstituted. The term “C3-C7-cycloalkyl-O-C2-C4-alkylene” refers to a radical group consisting of a “C3- C7-cycloalkyl” group bonded to an oxygen atom and the oxygen atom is bonded to a “C2-C4 alkylene” radical, wherein “C3-C7-cycloalkyl” and “C2-C4 alkylene” have the same definitions as described herein. Examples include, but are not limited to, 2-cyclopropoxyethyl (i.e., cyclopropyl-O- CH2CH2-), 2-cyclobutoxyethyl, 2-cyclopentyloxyethyl, 2-cyclohexyloxyethyl, 2-cycloheptyloxyethyl, 1-cyclopropoxyethyl (i.e., cyclopropyl-O-CH(CH3)-), 1-cyclobutoxyethyl, 1-cyclopentyloxyethyl, 1- cyclohexyloxyethyl, 1-cycloheptyloxyethyl, 3-cyclopropoxypropyl, 3-cyclobutoxypropyl, 3- cyclopentyloxypropyl, 3-cyclohexyloxypropyl, and 3-cycloheptyloxypropyl. It is understood that the chemical group “(cyclopropyl)methyl-d2” refers to the group in which the deuterium atoms are bonded to the methylene carbon (i.e., cyclopropyl-CD2-), for example, see Compound 99. When one or more substituents are present on the “C3-C7-cycloalkyl-O-C2-C4-alkylene” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “C3-C7-cycloalkyl-O-C2-C4- alkylene” group can be substituted or unsubstituted. The term “dialkylamino” refers to an amino group (-NH2) where the nitrogen is substituted with two “alkyl” groups. The two alkyl groups can be the same or different. The term “alkyl” has the same definition as described herein. The “dialkylamino” group can have 2 to 4 carbon atoms (i.e., “C2-C4-dialkylamino”) provided that the two alkyl groups do not exceed a total of 4 carbon atoms between the two groups. Examples include, dimethylamino (i.e., -N(Me)2), ethyl(methyl)amino (i.e., - N(Me)(Et)), diethylamino (i.e., -N(Et)2), and methyl(propyl)amino (i.e., -N(Me)(Propyl)). The term “haloalkyl” refers to an alkyl group, as defined herein, wherein one or more hydrogen atoms of the alkyl group have been replaced by a halogen atom. In some embodiments, the haloalkyl group can have 1 to 6 carbons (i.e., “C ₁ -C ₆ -haloalkyl”). The haloC ₁ -C ₆ alkyl can be fully substituted in which case it can be represented by the formula CnL2n+1, wherein L is a halogen and “n” is 1, 2, 3, 4, 5, or 6. When more than one halogen is present then they can be the same or different and selected from: fluorine, chlorine, bromine, and iodine. In some embodiments, haloalkyl contains 1 to 5 carbons (i.e., “C ₁ -C ₅ -haloalkyl”). In some embodiments, haloalkyl contains 1 to 4 carbons (i.e., “C ₁ -C ₄ -haloalkyl”). In some embodiments, haloalkyl contains 1 to 3 carbons (i.e., “C ₁ -C ₃ - haloalkyl”). In some embodiments, haloalkyl contains 1 or 2 carbons. Examples include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, chlorodifluoromethyl, 1-fluoroethyl, 2,2,2- trifluoroethyl, pentafluoroethyl, and 4,4,4-trifluorobutyl. The term “halogen” or “halo” refers to fluoro, chloro, bromo, or iodo group. In some embodiments, halogen or halo is fluoro, chloro, or bromo. In some embodiments, halogen or halo is fluoro or chloro. In some embodiments, halogen or halo is fluoro. The term “heterocyclyl” refers to a non-aromatic monocyclic ring system containing carbon atoms and at least one heteroatom. The heteroatom(s) include, but not limited to, oxygen, sulfur, and nitrogen, when more than one heteroatom is present in the ring the heteroatoms can be the same or different. In some embodiments, “3-7-membered-heterocyclyl” refers to a ring system containing 3 to 7 ring atoms, wherein at least one ring atom is a heteroatom. In some embodiments, “4-5- membered-heterocyclyl” refers to a ring system containing 4 or 5 ring atoms, wherein at least one ring atom is a heteroatom. In some embodiments, “4-7-membered-heterocyclyl” refers to a ring system containing 4 to 7 ring atoms, wherein at least one ring atom is a heteroatom. In some embodiments, “3-6-membered-heterocyclyl” refers to a ring system containing 3 to 6 ring atoms, wherein at least one ring atom is a heteroatom. In some embodiments, “4-6-membered-heterocyclyl” refers to a ring system containing 4 to 6 ring atoms, wherein at least one ring atom is a heteroatom. In some embodiments, the one or two heteroatoms in the ring system are selected independently from: O (oxygen) and N (nitrogen). In some embodiments, a heterocyclyl can include a carbonyl (C=O) group adjacent to a hetero atom, that is, be substituted with an oxo on a carbon adjacent to a hetero atom, where the substituted ring system is a lactam, lactone, cyclic imide, cyclic thioimide, or cyclic carbamate. Examples include, but are not limited to, aziridinyl, azetidinyl, piperidinyl, morpholinyl, oxetanyl, imidazolidinyl, piperazinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, and tetrahydrothiopyranyl. When one or more substituents are present on the “heterocyclyl” group, the substituent(s) can be bonded at any available carbon atom and/or heteroatom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “heterocyclyl” group can be substituted or unsubstituted. The term “4-8-membered-heterobicyclyl-C1-C4-alkylene” refers to a radical group consisting of a “4-8-membered-heterobicyclyl” group bonded to a “C1-C4 alkylene” radical, wherein “4-8-membered-heterobicyclyl” and “C1-C4 alkylene” have the same definitions as described herein. In some embodiments, the “4-8-membered-heterobicyclyl-C ₁ -C ₄ -alkylene” is a group selected from: (2-oxabicyclo[2.1.1]hexan-1-yl)methyl and (2-oxabicyclo[2.1.1]hexan-4- yl)methyl. When one or more substituents are present on the “4-8-membered-heterobicyclyl-C1-C4- alkylene” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “4-8- membered-heterobicyclyl-C ₁ -C ₄ -alkylene” group can be substituted or unsubstituted. The term “3-7-membered-heterocyclyl-C ₁ -C ₄ -alkylene” refers to a radical group consisting of a “3-7-membered-heterocyclyl” group bonded to a “C ₁ -C ₄ alkylene” radical, wherein “3-7- membered-heterocyclyl” and “C ₁ -C ₄ alkylene” have the same definitions as described herein. Examples include, but are not limited to, aziridin-1-ylmethyl(i.e., (aziridin-1-yl)CH ₂ -), aziridin-2- ylmethyl, azetidin-2-ylmethyl (i.e., (azetidin-2-yl)CH ₂ -), azetidin-3-ylmethyl (i.e., (azetidin-3-yl)CH ₂ - ), piperidinylmethyl, morpholinyl, oxetan-3-ylmethyl (i.e., (oxetan-3-yl)CH ₂ -), oxetan-2-ylmethyl (i.e., (oxetan-2-yl)CH ₂ -), 2-oxetan-3-ylethyl (i.e., (oxetan-3-yl)CH ₂ CH ₂ -), 2-oxetan-2-ylethyl (i.e., (oxetan-2-yl)CH ₂ CH ₂ -), imidazolidinylmethyl, piperazin-1-ylmethyl, piperazin-2-ylmethyl, pyrrolidin-3-ylmethyl, tetrahydrofuranylmethyl, tetrahydropyranylmethyl, and tetrahydrothiopyranylmethyl. In some embodiments, “3-7-membered-heterocyclyl-C1-C4-alkylene” is a group selected from: oxetan-3-ylmethyl (i.e., (oxetan-3-yl)CH2-), oxetan-2-ylmethyl (i.e., (oxetan- 2-yl)CH2-), 2-oxetan-3-ylethyl (i.e., (oxetan-3-yl)CH2CH2-), and 2-oxetan-2-ylethyl (i.e., (oxetan-2- yl)CH2CH2-). When one or more substituents are present on the “3-7-membered-heterocyclyl-C1-C4- alkylene” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “3-7- membered-heterocyclyl-C1-C4-alkylene” group can be substituted or unsubstituted. The term “spiro-cycloalkyl” refers to a non-aromatic, all carbon, bicyclic ring system where both rings are linked together by a single common ring carbon. In some embodiments, “C5-C11-spiro- cycloalkyl” refers to a spiro ring system containing 5 to 11 ring carbons. In some embodiments, “C5- C8-spiro-cycloalkyl” refers to a spiro ring system containing 5 to 8 ring carbons. In some embodiments, “C5-C7-spiro-cycloalkyl” refers to a spiro ring system containing 5 to 7 ring carbons. In some embodiments, “C7-spiro-cycloalkyl” refers to a spiro ring system containing 7 ring carbons (i.e., spiro[3.3]heptanyl and spiro[2.4]heptanyl). Examples include, but are not limited to, spiro[2.2]pentanyl, spiro[2.3]hexanyl, spiro[3.3]heptanyl, spiro[2.4]heptanyl, spiro[2.5]octanyl, spiro[3.4]octanyl, spiro[2.6]nonanyl, spiro[3.5]nonanyl, spiro[4.4]nonanyl, spiro[2.7]decanyl, spiro[3.6]decanyl, and spiro[4.5]decanyl. When one or more substituents are present on the “spiro- cycloalkyl” group, the substituent(s) can be bonded at any available carbon atom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “spiro-cycloalkyl” group can be substituted or unsubstituted. The term “spiro-heterocyclyl” refers to a bicyclic ring system containing carbon atoms and at least one heteroatom, where both rings are linked together by a single common ring carbon. In some embodiments, “5-11-membered-spiro-heterocyclyl” refers to a spiro ring system containing 5 to 11 ring atoms. In some embodiments, “5-8-membered-spiro-heterocyclyl” refers to a spiro ring system containing 5 to 8 ring atoms. In some embodiments, “5-7-membered-spiro-heterocyclyl” refers to a spiro ring system containing 5 to 7 ring atoms. Examples include, but are not limited to, azaspiro[2.2]pentanyl, azaspiro[2.3]hexanyl, oxaspiro[2.3]hexanyl, oxaspiro[3.3]heptanyl, azaspiro[3.3]heptanyl, azaspiro[3.4]octanyl, azaspiro[3.5]nonanyl, and oxaspiro[3.5]nonan-9-yl. When one or more substituents are present on the “spiro-heterocyclyl” group, the substituent(s) can be bonded at any available carbon atom and/or heteroatom. When more than one substituent is present, the substituents can be the same or different. In some embodiments, the “spiro-heterocyclyl” group can be substituted or unsubstituted. The term “hydroxyl” refers to the group -OH. As used herein, an “excipient” refers to a substance that is added to a composition to provide, without limitation, bulk, consistency, stability, binding ability, lubrication, disintegrating ability, etc., to the composition. A “diluent” is a type of excipient and refers to an ingredient in a pharmaceutical composition that lacks pharmacological activity but can be pharmaceutically necessary or desirable. For example, a diluent can be used to increase the bulk of a potent drug whose mass is too small for manufacture and/or administration. It can also be a liquid for the dissolution of a drug to be administered by injection, ingestion, or inhalation. A pharmaceutically acceptable excipient is a physiologically and pharmaceutically suitable non-toxic and inactive material or ingredient that does not interfere with the activity of the drug substance. Pharmaceutically acceptable excipients are well known in the pharmaceutical art and described, for example, in Rowe et al., Handbook of Pharmaceutical Excipients: A Comprehensive Guide to Uses, Properties, and Safety, 5th Ed., 2006, and in Remington: The Science and Practice of Pharmacy (Gennaro, 21st Ed. Mack Pub. Co., Easton, PA (2005)). Preservatives, stabilizers, dyes, buffers, and the like can be provided in the pharmaceutical composition. One skilled in this art can further formulate a compound as disclosed and described herein in an appropriate manner, and in accordance with accepted practices, such as, those disclosed in Remington, supra. As used herein, a “dose” or “dosage” refers to the measured quantity of drug substance to be taken at one time by a subject. In certain embodiments, wherein the drug substance is not a free base or free acid, the quantity is the molar equivalent to the corresponding amount of free base or free acid. As used herein, a “pharmaceutically acceptable salt” refers to a salt of a compound having an acidic or basic moiety which is not biologically or otherwise undesirable for use in a pharmaceutical product. In many cases, the compounds disclosed herein are capable of forming acid and/or base salts by virtue of the presence of an acidic or basic moiety (e.g., amino and/or carboxyl groups or groups similar thereto). Pharmaceutically acceptable acid addition salts can be formed by combining a compound having a basic moiety with inorganic acids and organic acids. Pharmaceutically acceptable base addition salts can be formed by combining a compound having an acidic moiety with inorganic and organic bases. The compounds described herein can have one or more stereocenters. All stereoisomers, such as, enantiomers and diastereomers, are intended unless otherwise indicated. It is understood that, in any compound described herein having one or more chiral centers, if an absolute stereochemistry is not expressly indicated, then each center can independently be the (R)-configuration, or the (S)- configuration, or a mixture thereof. Thus, the compounds provided herein can be enantiomerically pure, enantiomerically enriched, a racemic mixture, diastereomerically pure, diastereomerically enriched, or a stereoisomeric mixture. Preparation of enantiomerically pure or enantiomerically enriched forms can be accomplished by resolution of racemic mixtures or by using enantiomerically pure or enriched starting materials or by stereoselective or stereospecific synthesis. Stereochemical definitions are available in E.L. Eliel, S.H. Wilen & L.N. Mander, Stereochemistry of Organic Compounds, John Wiley & Sons, Inc., New York, NY, 1994 which is incorporated herein by reference in its entirety. In some embodiments, where the compound described herein is chiral or otherwise includes one or more stereocenters, the compound can be prepared with an enantiomeric excess or diastereomeric excess of greater than about 75%, greater than about 80%, greater than about 85%, greater than about 90%, greater than about 95%, greater than about 99%, greater than about 99.5%, or greater than about 99.9%. Resolution of racemic mixtures of compounds can be carried out by any of numerous methods known in the art. An example method includes fractional recrystallization using a chiral resolving organic acid with a racemic compound containing a basic group. Other chiral resolving agents suitable for fractional crystallization methods include stereoisomerically pure forms of methylbenzylamine (e.g., S and R forms, or diastereomerically pure forms), 2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine, cyclohexylethylamine, 1,2-diaminocyclohexane, and the like. Similarly, fractional recrystallization using a chiral resolving base can be utilized with a racemic compound containing a basic group. Resolution of racemic mixtures can also be carried out by elution on a chiral column. A suitable elution solvent composition can be determined by one skilled in the art. In some embodiments, a compound described herein can be prepared having at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 99%, at least about 99.5%, or at least about 99.9% enantiomeric excess, or an enantiomeric excess within a range defined by any of the preceding numbers. In some embodiments, a compound described herein can be prepared having at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99%, at least 99.5%, or at least 99.9% enantiomeric excess, or an enantiomeric excess within a range defined by any of the preceding numbers. In some embodiments, a compound described herein can be prepared having at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 99%, at least about 99.5%, or at least about 99.9% diastereomeric excess, or a diastereomeric excess within a range defined by any of the preceding numbers. In some embodiments, a compound described herein can be prepared having at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99%, at least 99.5%, or at least 99.9% diastereomeric excess, or a diastereomeric excess within a range defined by any of the preceding numbers. In addition, it is understood that, when a compound described herein contain one or more double bond(s) (e.g., C=C, C=N, and the like) or other centers of geometric asymmetry, and unless specified otherwise, it is understood that the compound includes both Z and E geometric isomers (e.g., cis or trans). Cis and trans geometric isomers of the compounds, as described herein, can be isolated as a mixture of isomers, or as separated isomeric form. The compounds described herein also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone – enol pairs, amide – imidic acid pairs, lactam – lactim pairs, enamine – imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H-imidazole, 1H-, 2H-, and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. The compounds described herein, and their pharmaceutically acceptable salts, can be found together with other substances, such as, water and solvents, for example, in the form of hydrates or solvates. When in the solid-state, the compounds described herein and salts thereof can occur in various forms and can, e.g., take the form of solvates, including hydrates. The compounds can be in any solid-state form, such as, a crystalline form, amorphous form, solvated form, etc. and unless clearly indicated otherwise, reference in the specification to compounds and salts thereof should be understood as reading on any solid-state form of the compound. The compounds described herein can be used in a neutral form, such as, a free acid or free base form. Alternatively, the compounds can be used in the form of pharmaceutically acceptable salts, such as, pharmaceutically acceptable addition salts of acids or bases. In some embodiments, the compounds described herein, or salts thereof, are substantially isolated. The phrase “substantially isolated” refers to the compound that is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compound described herein. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compound described herein, or salt thereof. ISOTOPES The compounds disclosed and described herein allow and embrace atoms at each position of the compound independently to have: 1) an isotopic distribution for a chemical element in proportional amounts to those usually found in nature or 2) an isotopic distribution in proportional amounts different to those usually found in nature unless the context clearly dictates otherwise. A particular chemical element has an atomic number defined by the number of protons within the atom's nucleus. Each atomic number identifies a specific chemical element, but not the isotope; an atom of a given element can have a wide range in its number of neutrons. The number of both protons and neutrons in the nucleus is the atom's mass number, and each isotope of a given element has a different mass number. Compounds wherein one or more atoms have an isotopic distribution for a chemical element in proportional amounts different to those usually found in nature is commonly referred to as being isotopically-labeled. Each chemical element as represented in a compound structure can include any isotopic distribution of said element. For example, in a compound structure a hydrogen atom can be explicitly disclosed or understood to be present in the compound. At any position of the compound that a hydrogen atom can be present, the hydrogen atom can be an isotopic distribution of hydrogen, including but not limited to protium ( ¹ H) and deuterium ( ² H) in proportional amounts to those usually found in nature and in proportional amounts different to those usually found in nature. Thus, reference herein to a compound encompasses all potential isotopic distributions for each atom unless the context clearly dictates otherwise. Examples of isotopes include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine, bromine, and iodine. As one of skill in the art would appreciate, any of the compounds as disclosed and described herein can include radioactive isotopes. Accordingly, also contemplated is use of compounds as disclosed and described herein, wherein one or more atoms have an isotopic distribution different to those usually found in nature, such as, having ² H or ³ H in greater proportion, or ¹¹ C, ¹³ C, or ¹⁴ C in greater proportion than found in nature. By way of general example, and without limitation, isotopes of hydrogen include protium ( ¹ H), deuterium ( ² H), and tritium ( ³ H). Isotopes of carbon include carbon-11 ( ¹¹ C), carbon-12 ( ¹² C), carbon-13 ( ¹³ C), and carbon-14 ( ¹⁴ C). Isotopes of nitrogen include nitrogen-13 ( ¹³ N), nitrogen-14 ( ¹⁴ N), and nitrogen- 15 ( ¹⁵ N). Isotopes of oxygen include oxygen-14 ( ¹⁴ O), oxygen-15 ( ¹⁵ O), oxygen-16 ( ¹⁶ O), oxygen-17 ( ¹⁷ O), and oxygen-18 ( ¹⁸ O). Isotopes of fluorine include fluorine-17 ( ¹⁷ F), fluorine-18 ( ¹⁸ F), and fluorine-19 ( ¹⁹ F). Isotopes of phosphorus include phosphorus-31 ( ³¹ P), phosphorus-32 ( ³² P), phosphorus-33 ( ³³ P), phosphorus-34 ( ³⁴ P), phosphorus-35 ( ³⁵ P), and phosphorus-36 ( ³⁶ P). Isotopes of sulfur include sulfur-32 ( ³² S), sulfur-33 ( ³³ S), sulfur-34 ( ³⁴ S), sulfur-35 ( ³⁵ S), sulfur-36 ( ³⁶ S), and sulfur-38 ( ³⁸ S). Isotopes of chlorine include chlorine-35 ( ³⁵ Cl), chlorine-36 ( ³⁶ Cl), and chlorine-37 ( ³⁷ Cl). Isotopes of bromine include bromine-75 ( ⁷⁵ Br), bromine-76 ( ⁷⁶ Br), bromine-77 ( ⁷⁷ Br), bromine- 79 ( ⁷⁹ Br), bromine-81 ( ⁸¹ Br), and bromine-82 ( ⁸² Br). Isotopes of iodine include iodine-123 ( ¹²³ I), iodine-124 ( ¹²⁴ I), iodine-125 ( ¹²⁵ I), iodine-131 ( ¹³¹ I), and iodine-135 ( ¹³⁵ I). In some embodiments, atoms at every position of the compound have an isotopic distribution for each chemical element in proportional amounts to those usually found in nature. In some embodiments, an atom in one position of the compound has an isotopic distribution for a chemical element in proportional amounts different to those usually found in nature (remainder atoms having an isotopic distribution for a chemical element in proportional amounts to those usually found in nature). In some embodiments, atoms in at least two positions of the compound independently have an isotopic distribution for a chemical element in proportional amounts different to those usually found in nature (remainder atoms having an isotopic distribution for a chemical element in proportional amounts to those usually found in nature). In some embodiments, atoms in at least three positions of the compound independently have an isotopic distribution for a chemical element in proportional amounts different to those usually found in nature (remainder atoms having an isotopic distribution for a chemical element in proportional amounts to those usually found in nature). In some embodiments, atoms in at least four positions of the compound independently have an isotopic distribution for a chemical element in proportional amounts different to those usually found in nature (remainder atoms having an isotopic distribution for a chemical element in proportional amounts to those usually found in nature). In some embodiments, atoms in at least five positions of the compound independently have an isotopic distribution for a chemical element in proportional amounts different to those usually found in nature (remainder atoms having an isotopic distribution for a chemical element in proportional amounts to those usually found in nature). In some embodiments, atoms in at least six positions of the compound independently have an isotopic distribution for a chemical element in proportional amounts different to those usually found in nature (remainder atoms having an isotopic distribution for a chemical element in proportional amounts to those usually found in nature). Certain compounds, for example those having incorporated radioactive isotopes, such as, ³ H and ¹⁴ C, are also useful in drug or substrate tissue distribution assays. Tritium ( ³ H) and carbon-14 ( ¹⁴ C) isotopes are particularly preferred for their ease of preparation and detectability. Compounds with isotopes, such as, deuterium ( ² H), in proportional amounts greater than usually found in nature can afford certain therapeutic advantages resulting from greater metabolic stability, such as, for example, increased in vivo half-life or reduced dosage requirements. Isotopically-labeled compounds can generally be prepared by performing procedures routinely practiced in the chemical art. Methods are readily available to measure such isotope perturbations or enrichments, such as, mass spectrometry, and for isotopes that are radio-isotopes additional methods are available, such as, radio- detectors used in connection with HPLC or GC. As used herein, “isotopic variant” means a compound that contains an unnatural proportion of an isotope at one or more of the atoms that constitute such a compound. In certain embodiments, an “isotopic variant” of a compound contains unnatural proportions of one or more isotopes, including, but not limited to, protium ( ¹ H), deuterium ( ² H), tritium ( ³ H), carbon-11 ( ¹¹ C), carbon-12 ( ¹² C), carbon-13 ( ¹³ C), carbon-14 ( ¹⁴ C), nitrogen-13 ( ¹³ N), nitrogen-14 ( ¹⁴ N), nitrogen-15 ( ¹⁵ N), oxygen-14 ( ¹⁴ O), oxygen-15 ( ¹⁵ O), oxygen-16 ( ¹⁶ O), oxygen-17 ( ¹⁷ O), oxygen-18 ( ¹⁸ O), fluorine-17 ( ¹⁷ F), fluorine-18 ( ¹⁸ F), phosphorus-31 ( ³¹ P), phosphorus-32 ( ³² P), phosphorus-33 ( ³³ P), sulfur-32 ( ³² S), sulfur-33 ( ³³ S), sulfur-34 ( ³⁴ S), sulfur-35 ( ³⁵ S), sulfur-36 ( ³⁶ S), chlorine-35 ( ³⁵ Cl), chlorine-36 ( ³⁶ Cl), chlorine-37 ( ³⁷ Cl), bromine-79 ( ⁷⁹ Br), bromine-81 ( ⁸¹ Br), iodine-123 ( ¹²³ I), iodine-125 ( ¹²⁵ I), iodine- 127 ( ¹²⁷ I), iodine-129 ( ¹²⁹ I), and iodine-131 ( ¹³¹ I). In certain embodiments, an “isotopic variant” of a compound is in a stable form, that is, non-radioactive. In certain embodiments, an “isotopic variant” of a compound contains unnatural proportions of one or more isotopes, including, but not limited to, hydrogen ( ¹ H), deuterium ( ² H), carbon-12 ( ¹² C), carbon-13 ( ¹³ C), nitrogen-14 ( ¹⁴ N), nitrogen-15 ( ¹⁵ N), oxygen-16 ( ¹⁶ O), oxygen-17 ( ¹⁷ O), and oxygen-18 ( ¹⁸ O). In certain embodiments, an “isotopic variant” of a compound is in an unstable form, that is, radioactive. In certain embodiments, an “isotopic variant” of a compound described herein contains unnatural proportions of one or more isotopes, including, but not limited to, tritium ( ³ H), carbon-11 ( ¹¹ C), carbon-14 ( ¹⁴ C), nitrogen-13 ( ¹³ N), oxygen-14 ( ¹⁴ O), and oxygen-15 ( ¹⁵ O). It will be understood that, in a compound as provided herein, any hydrogen can include ² H as the major isotopic form, as example, or any carbon include be ¹³ C as the major isotopic form, as example, or any nitrogen can include ¹⁵ N as the major isotopic form, as example, and any oxygen can include ¹⁸ O as the major isotopic form, as example. In certain embodiments, an “isotopic variant” of a compound contains an unnatural proportion of deuterium ( ² H). With regard to the compounds provided herein, when a particular atomic position is designated as having deuterium or “D” or “d”, it is understood that the abundance of deuterium at that position is substantially greater than the natural abundance of deuterium, which is about 0.015%. A position designated as having deuterium typically has a minimum isotopic enrichment factor of, in certain embodiments, at least 3500 (52.5% deuterium incorporation), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation) at each designated deuterium position. Similarly, with regard to the compounds provided herein when any atomic position is designated as a specific isotope, it is understood that the abundance of the specific isotope at that position is substantially greater than the natural abundance of that isotope. A position designated as having a specific isotope typically has a minimum isotopic enrichment factor of, in certain embodiments, at least 52.5%, at least 60%, at least 67.5%, at least 75%, at least 82.5%, at least 90%, at least 95%, at least 97%, at least 99%, or at least 99.5% incorporation of the isotope at each designated position. Synthetic methods for incorporating radio-isotopes into organic compounds are applicable to compound described herein and are well known in the art. These synthetic methods, for example, incorporating activity levels of tritium into target molecules, are as follows: A. Catalytic Reduction with Tritium Gas: This procedure normally yields high specific activity products and requires halogenated or unsaturated precursors. B. Reduction with Sodium Borohydride [ ³ H]: This procedure is rather inexpensive and requires precursors containing reducible functional groups, such as, aldehydes, ketones, lactones, esters, and the like. C. Reduction with Lithium Aluminum Hydride [ ³ H]: This procedure offers products at almost theoretical specific activities. It also requires precursors containing reducible functional groups, such as, aldehydes, ketones, lactones, esters, and the like. D. Tritium Gas Exposure Labeling: This procedure involves exposing precursors containing exchangeable protons to tritium gas in the presence of a suitable catalyst. E. N-Methylation using Methyl Iodide [ ³ H]: This procedure is usually employed to prepare O- methyl or N-methyl ( ³ H) products by treating appropriate precursors with high specific activity methyl iodide ( ³ H). This method in general allows for higher specific activity, such as, for example, about 70- 90 Ci/mmol. Synthetic methods for incorporating activity levels of ¹²⁵ I into target molecules include: A. Sandmeyer and like reactions: This procedure transforms an aryl amine or a heteroaryl amine into a diazonium salt, such as, a diazonium tetrafluoroborate salt and subsequently to ¹²⁵ I labeled compound using Na ¹²⁵ I. A representative procedure was reported by Zhu, G-D. and co- workers in J. Org. Chem., 2002, 67, 943-948. B. Ortho ¹²⁵ Iodination of phenols: This procedure allows for the incorporation of ¹²⁵ I at the ortho position of a phenol as reported by Collier, T. L. and co-workers in J. Labelled Compd. Radiopharm., 1999, 42, S264-S266. C. Aryl and heteroaryl bromide exchange with ¹²⁵ I: This method is generally a two-step process. The first step is the conversion of the aryl or heteroaryl bromide to the corresponding tri- alkyltin intermediate using for example, a Pd catalyzed reaction [i.e. Pd(Ph3P)4] or through an aryl or heteroaryl lithium, in the presence of a tri-alkyltinhalide or hexaalkylditin [e.g., (CH3)3SnSn(CH3)3]. A representative procedure was reported by Le Bas, M.-D. and co-workers in J. Labelled Compd. Radiopharm., 2001, 44, S280-S282. A radiolabeled form of a compound described herein can be used in a screening assay to identify/evaluate compounds. In general terms, a newly synthesized or identified compound (i.e., test compound) can be evaluated for its ability to reduce binding of a radiolabeled form of a compound disclosed herein to VMAT2. The ability of a test compound to compete with a radiolabeled form of a compound described herein for the binding to VMAT2 correlates to its binding affinity. COMPOUNDS One aspect of the present disclosure encompasses, inter alia, a compound of Formula (Ia): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ is selected from: C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene, C ₁ -C ₆ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₁ -C ₄ - alkyl-O-C ₂ -C ₄ -alkylene, C ₃ -C ₇ -cycloalkyl-O-C ₂ -C ₄ -alkylene, 3-7-membered-heterocyclyl, 3-7- membered-heterocyclyl-C ₁ -C ₄ -alkylene, C ₄ -C ₈ -bicycloalkyl-C ₁ -C ₄ -alkylene, C ₄ -C ₇ -cycloalkenyl, 5- 11-membered-spiro-heterocyclyl, C ₅ -C ₁₁ -spiro-cycloalkyl, cubanyl-C ₁ -C ₄ -alkylene, and 4-8- membered-heterobicyclyl-C ₁ -C ₄ -alkylene; wherein each R ¹ group is optionally substituted with one or more substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, cyano, C ₁ -C ₄ -alkylsulfonyl, C ₃ -C ₆ - cycloalkyl, hydroxyl, C ₁ -C ₄ -alkoxy, and C ₂ -C ₄ -dialkylamino. Another aspect of the present disclosure encompasses, inter alia, a compound of Formula (Ia): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ is selected from: C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene, C ₁ -C ₆ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₁ -C ₄ - alkyl-O-C ₂ -C ₄ -alkylene, C ₃ -C ₇ -cycloalkyl-O-C ₂ -C ₄ -alkylene, 3-7-membered-heterocyclyl, 3-7- membered-heterocyclyl-C ₁ -C ₄ -alkylene, C ₄ -C ₈ -bicycloalkyl-C ₁ -C ₄ -alkylene, C ₄ -C ₇ -cycloalkenyl, 5- 11-membered-spiro-heterocyclyl, and C ₅ -C ₁₁ -spiro-cycloalkyl; wherein each R ¹ group is optionally substituted with one or more substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, cyano, C ₁ -C ₄ -alkylsulfonyl, C ₃ -C ₆ - cycloalkyl, hydroxyl, C ₁ -C ₄ -alkoxy, and C ₂ -C ₄ -dialkylamino. In some embodiments, the R ¹ group is optionally substituted with one, two, three, four, five, six, seven, or eight substituents. In some embodiments, the R ¹ group is optionally substituted with one, two, three, four, five, six, or seven substituents. In some embodiments, the R ¹ group is optionally substituted with one, two, three, four, five, or six substituents. In some embodiments, the R ¹ group is optionally substituted with one, two, three, four, or five substituents. In some embodiments, the R ¹ group is optionally substituted with one, two, three, or four substituents. In some embodiments, the R ¹ group is optionally substituted with one, two, or three substituents. In some embodiments, the R ¹ group is optionally substituted with one or two substituents. In some embodiments, the R ¹ group is optionally substituted with one substituent. In some embodiments, the R ¹ group is not substituted. In some embodiments, the R ¹ group is substituted with one, two, three, four, five, six, seven, or eight substituents. In some embodiments, the R ¹ group is substituted with one, two, three, four, five, six, or seven substituents. In some embodiments, the R ¹ group is substituted with one, two, three, four, five, or six substituents. In some embodiments, the R ¹ group is substituted with one, two, three, four, or five substituents. In some embodiments, the R ¹ group is substituted with one, two, three, or four substituents. In some embodiments, the R ¹ group is substituted with one, two, or three substituents. In some embodiments, the R ¹ group is substituted with one or two substituents. In some embodiments, the R ¹ group is substituted with one substituent. Some embodiments provide a compound of Formula (Ic): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ has the same definition as described herein, supra, and infra. It is understood that the stereochemistry for compounds of Formula (Ic) includes both the 2S,3R,11bR isomer and the 2R,3R,11bR isomer. Some embodiments provide a compound of Formula (Ie): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ has the same definition as described herein, supra, and infra. The stereochemistry for a compound of Formula (Ie) is the 2R,3R,11bR isomer. Some embodiments provide a compound of Formula (Ig): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ has the same definition as described herein, supra, and infra. The stereochemistry for a compound of Formula (Ig) is the 2S,3R,11bR isomer. Some embodiments provide a compound of Formula (Ii): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ has the same definition as described herein, supra, and infra. The stereochemistry for a compound of Formula (Ii) is the 2R,3S,11bS isomer. Some embodiments provide a compound of Formula (Ik): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ has the same definition as described herein, supra, and infra. The stereochemistry for a compound of Formula (Ik) is the 2S,3S,11bS isomer. Some embodiments provide a compound, as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound has an elimination t _1/2 ≥ 420 minutes as determined using a human liver microsomes (HLM) assay, such as, the assay as described in Example 17. In some embodiments, the compound has an elimination t _1/2 ≥ 400 minutes. In some embodiments, the compound has an elimination t _1/2 ≥ 375 minutes. In some embodiments, the compound has an elimination t _1/2 ≥ 350 minutes. In some embodiments, the compound has an elimination t _1/2 ≥ 325 minutes. In some embodiments, the compound has an elimination t _1/2 ≥ 300 minutes. In some embodiments, the compound has an elimination t _1/2 ≥ 275 minutes. In some embodiments, the compound has an elimination t1/2 ≥ 250 minutes. In some embodiments, the compound has an elimination t _1/2 ≥ 225 minutes. In some embodiments, the compound has an elimination t _1/2 ≥ 200 minutes. Some embodiments provide a compound, as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound has an IC50 > 6,000 nM against CYP2D6 and CYP3A4, as determined using an IC50 method, such as, the method described in Example 18. In some embodiments, the compound has an IC50 > 5,000 nM against CYP2D6. In some embodiments, the compound has an IC50 > 4,000 nM against CYP2D6. In some embodiments, the compound has an IC50 > 3,000 nM against CYP2D6. In some embodiments, the compound has an IC50 > 2,000 nM against CYP2D6. In some embodiments, the compound has an IC ₅₀ > 5,000 nM against CYP3A4. In some embodiments, the compound has an IC ₅₀ > 4,000 nM against CYP3A4. In some embodiments, the compound has an IC ₅₀ > 3,000 nM against CYP3A4. In some embodiments, the compound has an IC ₅₀ > 2,000 nM against CYP3A4. In some embodiments, the compound is substantially inactive against CYP2D6. In some embodiments, the compound is substantially inactive against CYP3A4. Some embodiments provide a compound, as described herein, or a pharmaceutically acceptable salt thereof, wherein the compound has an IC ₅₀ > 12,000 nM against hERG (human ether- a-go-go-related gene) as determined using an IC ₅₀ method, such as, the method described in Example 19. In some embodiments, the compound has an IC50 > 11,000 nM against hERG. In some embodiments, the compound has an IC50 > 10,000 nM against hERG. In some embodiments, the compound has an IC50 > 9,000 nM against hERG. In some embodiments, the compound has an IC50 > 8,000 nM against hERG. In some embodiments, the compound has an IC50 > 7,000 nM against hERG. In some embodiments, the compound is substantially inactive against hERG. The phrase “compound as described herein” or “compounds as described herein” refers to any compound or compounds in the present disclosure, supra, and infra. In some embodiments, the compound(s) is of Formula (Ia). In some embodiments, the compound(s) is of Formula (Ic). In some embodiments, the compound(s) is of Formula (Ie). In some embodiments, the compound(s) is of Formula (Ig). In some embodiments, the compound(s) is of Formula (Ii). In some embodiments, the compound(s) is of Formula (Ik). In some embodiments, R ¹ is selected from: C3-C7-cycloalkyl-C1-C4-alkylene, C1-C6-alkyl, C3- C7-cycloalkyl, C1-C4-alkyl-O-C2-C4-alkylene, C3-C7-cycloalkyl-O-C2-C4-alkylene, 3-7-membered- heterocyclyl, 3-7-membered-heterocyclyl-C1-C4-alkylene, C4-C8-bicycloalkyl-C1-C4-alkylene, C4-C7- cycloalkenyl, 5-11-membered-spiro-heterocyclyl, C5-C11-spiro-cycloalkyl, cubanyl-C1-C4-alkylene, and 4-8-membered-heterobicyclyl-C1-C4-alkylene; wherein each R ¹ group is optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C3-C6-cycloalkyl, hydroxyl, and C1-C4-alkoxy. In some embodiments, R ¹ is selected from: C3-C7-cycloalkyl-C1-C4-alkylene, C1-C6-alkyl, C3- C7-cycloalkyl, C1-C4-alkyl-O-C2-C4-alkylene, C3-C7-cycloalkyl-O-C2-C4-alkylene, 3-7-membered- heterocyclyl, 3-7-membered-heterocyclyl-C1-C4-alkylene, C4-C8-bicycloalkyl-C1-C4-alkylene, C4-C7- cycloalkenyl, 5-11-membered-spiro-heterocyclyl, and C ₅ -C ₁₁ -spiro-cycloalkyl; wherein each R ¹ group is optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C3-C6-cycloalkyl, hydroxyl, and C ₁ -C ₄ -alkoxy. In some embodiments, R ¹ is selected from: C ₃ -C ₅ -cycloalkyl-C ₁ -C ₂ -alkylene, C ₁ -C ₅ -alkyl, C ₃ - C ₅ -cycloalkyl, C ₁ -C ₃ -alkyl-O-CH ₂ CH ₂ -, cyclopropyl-O-CH ₂ CH ₂ -, 4-5-membered-heterocyclyl, (4- membered-heterocyclyl)CH ₂ -, (C ₅ -C ₆ -bicycloalkyl)CH ₂ -, C ₄ -cycloalkenyl, 7-membered-spiro- heterocyclyl, C ₇ -spiro-cycloalkyl, (cubanyl)CH ₂ -, and 6-membered-heterobicyclyl-C ₁ -C ₄ -alkylene- CH ₂ -; wherein each R ¹ group is optionally substituted with one or more substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, cyano, C ₃ -C ₆ -cycloalkyl, hydroxyl, and C ₁ -C ₄ -alkoxy. In some embodiments, R ¹ is selected from: C ₃ -C ₅ -cycloalkyl-C ₁ -C ₂ -alkylene, C ₁ -C ₅ -alkyl, C ₃ - C ₅ -cycloalkyl, C ₁ -C ₃ -alkyl-O-CH ₂ CH ₂ -, cyclopropyl-O-CH ₂ CH ₂ -, 4-5-membered-heterocyclyl, (4- membered-heterocyclyl)CH ₂ -, (C ₅ -bicycloalkyl)CH ₂ -, C ₄ -cycloalkenyl, 7-membered-spiro- heterocyclyl, and C7-spiro-cycloalkyl; wherein each R ¹ group is optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C3-C6-cycloalkyl, hydroxyl, and C1-C4-alkoxy. In some embodiments, R ¹ is selected from: C3-C5-cycloalkyl-C1-C2-alkylene, C1-C5-alkyl, C3- C5-cycloalkyl, C1-C3-alkyl-O-CH2CH2-, cyclopropyl-O-CH2CH2-, 4-5-membered-heterocyclyl, (4- membered-heterocyclyl)CH2-, (C5-C6-bicycloalkyl)CH2-, C4-cycloalkenyl, 7-membered-spiro- heterocyclyl, C7-spiro-cycloalkyl, (cubanyl)CH2-, and 6-membered-heterobicyclyl-C1-C4-alkylene- CH2-; wherein each R ¹ group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, methyl, C1-haloalkyl, cyano, cyclopropyl, hydroxyl, and methoxy. In some embodiments, R ¹ is selected from: C3-C5-cycloalkyl-C1-C2-alkylene, C1-C5-alkyl, C3- C5-cycloalkyl, C1-C3-alkyl-O-CH2CH2-, cyclopropyl-O-CH2CH2-, 4-5-membered-heterocyclyl, (4- membered-heterocyclyl)CH2-, (C5-bicycloalkyl)CH2-, C4-cycloalkenyl, 7-membered-spiro- heterocyclyl, and C7-spiro-cycloalkyl; wherein each R ¹ group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, methyl, C1-haloalkyl, cyano, cyclopropyl, hydroxyl, and methoxy. In some embodiments, R ¹ is selected from: C3-C5-cycloalkyl-C1-C2-alkylene, C1-C5-alkyl, C3- C5-cycloalkyl, C1-C3-alkyl-O-CH2CH2-, cyclopropyl-O-CH2CH2-, 4-5-membered-heterocyclyl, (4- membered-heterocyclyl)CH2-, (C5-C6-bicycloalkyl)CH2-, C4-cycloalkenyl, 7-membered-spiro- heterocyclyl, C7-spiro-cycloalkyl, (cubanyl)CH2-, and 6-membered-heterobicyclyl-C1-C4-alkylene- CH2-; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, methyl, C ₁ -haloalkyl, cyano, cyclopropyl, hydroxyl, and methoxy. In some embodiments, R ¹ is selected from: C ₃ -C ₅ -cycloalkyl-C ₁ -C ₂ -alkylene, C ₁ -C ₅ -alkyl, C ₃ - C ₅ -cycloalkyl, C ₁ -C ₃ -alkyl-O-CH ₂ CH ₂ -, cyclopropyl-O-CH ₂ CH ₂ -, 4-5-membered-heterocyclyl, (4- membered-heterocyclyl)CH ₂ -, (C ₅ -bicycloalkyl)CH ₂ -, C ₄ -cycloalkenyl, 7-membered-spiro- heterocyclyl, and C ₇ -spiro-cycloalkyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, methyl, C ₁ -haloalkyl, cyano, cyclopropyl, hydroxyl, and methoxy. In some embodiments, R ¹ is selected from: C ₃ -C ₅ -cycloalkyl-C ₁ -C ₂ -alkylene, C ₁ -C ₅ -alkyl, C ₃ - C ₅ -cycloalkyl, C ₁ -C ₃ -alkyl-O-CH ₂ CH ₂ -, cyclopropyl-O-CH ₂ CH ₂ -, 4-membered-heterocyclyl, (4- membered-heterocyclyl)CH ₂ -, (C ₅ -C ₆ -bicycloalkyl)CH ₂ -, C ₄ -cycloalkenyl, 7-membered-spiro- heterocyclyl, C ₇ -spiro-cycloalkyl, (cubanyl)CH ₂ -, and 6-membered-heterobicyclyl-C ₁ -C ₄ -alkylene- CH ₂ -; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, methyl, C1-haloalkyl, cyano, cyclopropyl, hydroxyl, and methoxy. In some embodiments, R ¹ is selected from: C3-C5-cycloalkyl-C1-C2-alkylene, C1-C5-alkyl, C3- C5-cycloalkyl, C1-C3-alkyl-O-CH2CH2-, cyclopropyl-O-CH2CH2-, 4-membered-heterocyclyl, (4- membered-heterocyclyl)CH2-, (C5-bicycloalkyl)CH2-, C4-cycloalkenyl, 7-membered-spiro- heterocyclyl, and C7-spiro-cycloalkyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, methyl, C1-haloalkyl, cyano, cyclopropyl, hydroxyl, and methoxy. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, cyclopropoxyethyl, methyl, methyl-d3, ethyl, ethyl-d5, cyclopropyl, isopropyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, neopentyl, cyclobutenyl, oxaspiro[3.3]heptanyl, spiro[3.3]heptanyl, pyrrolidinyl, (cyclobutyl)ethyl, (cubanyl)methyl, (bicyclo[2.1.1]hexanyl)methyl, (silolanyl)methyl, and (2-oxabicyclo[2.1.1]hexanyl)methyl; wherein each group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, dimethylamino, methylsulfonyl, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, cyclopropoxyethyl, methyl, ethyl, cyclopropyl, isopropyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, neopentyl, cyclobutenyl, oxaspiro[3.3]heptanyl, spiro[3.3]heptanyl, pyrrolidinyl, and (cyclobutyl)ethyl; wherein each group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, dimethylamino, methylsulfonyl, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, cyclopropoxyethyl, methyl, methyl-d ₃ , ethyl, ethyl-d ₅ , cyclopropyl, isopropyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, neopentyl, cyclobutenyl, oxaspiro[3.3]heptanyl, spiro[3.3]heptanyl, pyrrolidinyl, and (cyclobutyl)ethyl, (cubanyl)methyl, (bicyclo[2.1.1]hexanyl)methyl, (silolanyl)methyl, and (2-oxabicyclo[2.1.1]hexanyl)methyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, dimethylamino, methylsulfonyl, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, cyclopropoxyethyl, methyl, ethyl, cyclopropyl, isopropyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, neopentyl, cyclobutenyl, oxaspiro[3.3]heptanyl, spiro[3.3]heptanyl, pyrrolidinyl, and (cyclobutyl)ethyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, dimethylamino, methylsulfonyl, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, cyclopropoxyethyl, methyl, methyl-d3, ethyl, ethyl-d5, cyclopropyl, isopropyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, neopentyl, cyclobutenyl, oxaspiro[3.3]heptanyl, spiro[3.3]heptanyl, (cyclobutyl)ethyl, (cubanyl)methyl, (bicyclo[2.1.1]hexanyl)methyl, (silolanyl)methyl, and (2- oxabicyclo[2.1.1]hexanyl)methyl; wherein each group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, cyclopropoxyethyl, methyl, ethyl, cyclopropyl, isopropyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, neopentyl, cyclobutenyl, oxaspiro[3.3]heptanyl, spiro[3.3]heptanyl, and (cyclobutyl)ethyl; wherein each group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, cyclopropoxyethyl, methyl, methyl-d ₃ , ethyl, ethyl-d ₅ , cyclopropyl, isopropyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, neopentyl, cyclobutenyl, oxaspiro[3.3]heptanyl, spiro[3.3]heptanyl, (cyclobutyl)ethyl, (cubanyl)methyl, (bicyclo[2.1.1]hexanyl)methyl, (silolanyl)methyl, and (2- oxabicyclo[2.1.1]hexanyl)methyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, cyclopropoxyethyl, methyl, ethyl, cyclopropyl, isopropyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, neopentyl, cyclobutenyl, oxaspiro[3.3]heptanyl, spiro[3.3]heptanyl, and (cyclobutyl)ethyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, isopentyl, cyclobutyl, 2- methoxyethyl, butyl, propyl, 2-cyclopropoxyethyl, methyl, methyl-d3, ethyl, ethyl-d5, cyclopropyl, isopropyl, 2-((propan-2-yl)oxy)ethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3- methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1-yl)methyl, 2-(methoxy)ethyl, neopentyl, cyclobut-2- en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, spiro[3.3]heptan-2-yl, pyrrolidin-3-yl, 1-(cyclobutyl)ethyl, (cuban-1-yl)methyl, (bicyclo[2.1.1]hexan-1-yl)methyl, (silolan-3-yl)methyl, (2- oxabicyclo[2.1.1]hexan-1-yl)methyl, and (2-oxabicyclo[2.1.1]hexan-4-yl)methyl; wherein each group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, dimethylamino, methylsulfonyl, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, isopentyl, cyclobutyl, 2-methoxyethyl, butyl, propyl, 2- cyclopropoxyethyl, methyl, ethyl, cyclopropyl, isopropyl, 2-((propan-2-yl)oxy)ethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3-methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1- yl)methyl, 2-(methoxy)ethyl, neopentyl, cyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, spiro[3.3]heptan-2-yl, pyrrolidin-3-yl, and 1-(cyclobutyl)ethyl; wherein each group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, dimethylamino, methylsulfonyl, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , isopentyl, cyclobutyl, 2- methoxyethyl, butyl, propyl, 2-cyclopropoxyethyl, methyl, methyl-d ₃ , ethyl, ethyl-d ₅ , cyclopropyl, isopropyl, 2-((propan-2-yl)oxy)ethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3- methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1-yl)methyl, 2-(methoxy)ethyl, neopentyl, cyclobut-2- en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, spiro[3.3]heptan-2-yl, pyrrolidin-3-yl, 1-(cyclobutyl)ethyl, (cuban-1-yl)methyl, (bicyclo[2.1.1]hexan-1-yl)methyl, (silolan-3-yl)methyl, (2- oxabicyclo[2.1.1]hexan-1-yl)methyl, and (2-oxabicyclo[2.1.1]hexan-4-yl)methyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, dimethylamino, methylsulfonyl, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, isopentyl, cyclobutyl, 2-methoxyethyl, butyl, propyl, 2- cyclopropoxyethyl, methyl, ethyl, cyclopropyl, isopropyl, 2-((propan-2-yl)oxy)ethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3-methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1- yl)methyl, 2-(methoxy)ethyl, neopentyl, cyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, spiro[3.3]heptan-2-yl, pyrrolidin-3-yl, and 1-(cyclobutyl)ethyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, dimethylamino, methylsulfonyl, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, isopentyl, cyclobutyl, 2- methoxyethyl, butyl, propyl, 2-cyclopropoxyethyl, methyl, methyl-d3, ethyl, ethyl-d5, cyclopropyl, isopropyl, 2-((propan-2-yl)oxy)ethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3- methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1-yl)methyl, 2-(methoxy)ethyl, neopentyl, cyclobut-2- en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, spiro[3.3]heptan-2-yl, 1-(cyclobutyl)ethyl, (cuban-1-yl)methyl, (bicyclo[2.1.1]hexan-1-yl)methyl, (silolan-3-yl)methyl, (2-oxabicyclo[2.1.1]hexan-1-yl)methyl, and (2-oxabicyclo[2.1.1]hexan-4-yl)methyl; wherein each group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, isopentyl, cyclobutyl, 2-methoxyethyl, butyl, propyl, 2- cyclopropoxyethyl, methyl, ethyl, cyclopropyl, isopropyl, 2-((propan-2-yl)oxy)ethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3-methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1- yl)methyl, 2-(methoxy)ethyl, neopentyl, cyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, spiro[3.3]heptan-2-yl, and 1-(cyclobutyl)ethyl; wherein each group is optionally substituted with one or more substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , isopentyl, cyclobutyl, 2- methoxyethyl, butyl, propyl, 2-cyclopropoxyethyl, methyl, methyl-d3, ethyl, ethyl-d5, cyclopropyl, isopropyl, 2-((propan-2-yl)oxy)ethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3- methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1-yl)methyl, 2-(methoxy)ethyl, neopentyl, cyclobut-2- en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, spiro[3.3]heptan-2-yl, 1-(cyclobutyl)ethyl, (cuban-1-yl)methyl, (bicyclo[2.1.1]hexan-1-yl)methyl, (silolan-3-yl)methyl, (2-oxabicyclo[2.1.1]hexan-1-yl)methyl, and (2-oxabicyclo[2.1.1]hexan-4-yl)methyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (cyclopropyl)methyl, isopentyl, cyclobutyl, 2-methoxyethyl, butyl, propyl, 2- cyclopropoxyethyl, methyl, ethyl, cyclopropyl, isopropyl, 2-((propan-2-yl)oxy)ethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3-methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1- yl)methyl, 2-(methoxy)ethyl, neopentyl, cyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, spiro[3.3]heptan-2-yl, and 1-(cyclobutyl)ethyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: cyanomethyl, fluoro, cyano, hydroxyl, difluoromethyl, methyl, trifluoromethyl, methoxy, and cyclopropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (1-(cyanomethyl)cyclopropyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2-(cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2- cyclopropoxyethyl, 2-fluoro-2-methylpropyl, methyl, methyl-d3, 2,2-difluoropropyl, 2,2,2- trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, 2-hydroxypropyl, ethyl, ethyl-d ₅ , isopropyl, 2-methoxyethyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , 3- fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, (oxetan-2-yl)methyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, (2,2-difluorocyclopropyl)methyl, 2-(trifluoromethoxy)ethyl, neopentyl, (1- methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, 3- fluorocyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, 3-cyanocyclobutyl, 3-fluorocyclobutyl, 3,3- dimethylcyclobutyl, spiro[3.3]heptan-2-yl, 1-methylpyrrolidin-3-yl, (3-methyloxetan-3-yl)methyl, (1- methylcyclopropyl)methyl, 1-methylcyclobutyl, (2-fluorocyclopropyl)methyl, (2,2-difluoro-3- methylcyclopropyl)methyl, 1-cyclobutylethyl, (2,2-dimethylcyclopropyl)methyl, (3,3- difluorocyclopentyl)methyl, 3-(trifluoromethyl)cyclobutyl, 2-fluoropropyl, 3-methoxycyclobutyl, 3- (dimethylamino)cyclobutyl, cyanomethyl, (1-cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, 2-methoxypropyl, (1-(methylsulfonyl)cyclopropyl)methyl, 3-(methylsulfonyl)propyl, 2- (methylsulfonyl)ethyl, 3,3-difluorocyclobutyl (2,2-difluorocyclobutyl)methyl, (cuban-1-yl)methyl, (bicyclo[1.1.1]pentan-1-yl)methyl, (bicyclo[2.1.1]hexan-1-yl)methyl, (1,1-dimethylsilolan-3- yl)methyl, (3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)methyl, (2-oxabicyclo[2.1.1]hexan-1- yl)methyl, and (2-oxabicyclo[2.1.1]hexan-4-yl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (1-(cyanomethyl)cyclopropyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2-(cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2- cyclopropoxyethyl, 2-fluoro-2-methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3- trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, 2-hydroxypropyl, ethyl, isopropyl, 2- methoxyethyl, (cyclopropyl)methyl, 3-fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, (oxetan-2-yl)methyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3- fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, (2,2-difluorocyclopropyl)methyl, 2- (trifluoromethoxy)ethyl, neopentyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2- difluorocyclopentyl)methyl, 3-fluorocyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, 3- cyanocyclobutyl, 3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, 1- methylpyrrolidin-3-yl, (3-methyloxetan-3-yl)methyl, (1-methylcyclopropyl)methyl, 1- methylcyclobutyl, (2-fluorocyclopropyl)methyl, (2,2-difluoro-3-methylcyclopropyl)methyl, 1- cyclobutylethyl, (2,2-dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, 3- (trifluoromethyl)cyclobutyl, 2-fluoropropyl, 3-methoxycyclobutyl, 3-(dimethylamino)cyclobutyl, cyanomethyl, (1-cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, 2-methoxypropyl, (1- (methylsulfonyl)cyclopropyl)methyl, 3-(methylsulfonyl)propyl, 2-(methylsulfonyl)ethyl, 3,3- difluorocyclobutyl, and (2,2-difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (1-(cyanomethyl)cyclopropyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2-(cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2- cyclopropoxyethyl, 2-fluoro-2-methylpropyl, methyl, methyl-d ₃ , 2,2-difluoropropyl, 2,2,2- trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, 2-hydroxypropyl, ethyl, ethyl-d ₅ , isopropyl, 2-methoxyethyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , 3- fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, (oxetan-2-yl)methyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, (2,2-difluorocyclopropyl)methyl, 2-(trifluoromethoxy)ethyl, neopentyl, (1- methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, 3- fluorocyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, 3-cyanocyclobutyl, 3-fluorocyclobutyl, 3,3- dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (3-methyloxetan-3-yl)methyl, (1- methylcyclopropyl)methyl, 1-methylcyclobutyl, (2-fluorocyclopropyl)methyl, (2,2-difluoro-3- methylcyclopropyl)methyl, 1-cyclobutylethyl, (2,2-dimethylcyclopropyl)methyl, (3,3- difluorocyclopentyl)methyl, 3-(trifluoromethyl)cyclobutyl, 2-fluoropropyl, 3-methoxycyclobutyl, cyanomethyl, (1-cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, 2-methoxypropyl, 3,3- difluorocyclobutyl, (2,2-difluorocyclobutyl)methyl, (cuban-1-yl)methyl, (bicyclo[1.1.1]pentan-1- yl)methyl, (bicyclo[2.1.1]hexan-1-yl)methyl, (1,1-dimethylsilolan-3-yl)methyl, (3- (trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)methyl, (2-oxabicyclo[2.1.1]hexan-1-yl)methyl, and (2- oxabicyclo[2.1.1]hexan-4-yl)methyl. In some embodiments, R ¹ is (cyclopentyl)methyl. In some embodiments, R ¹ is isobutyl. In some embodiments, R ¹ is cyclopentyl. In some embodiments, R ¹ is (cyclobutyl)methyl. In some embodiments, R ¹ is (1-(cyanomethyl)cyclopropyl)methyl. In some embodiments, R ¹ is isopentyl. In some embodiments, R ¹ is (1-fluorocyclobutyl)methyl. In some embodiments, R ¹ is cyclobutyl. In some embodiments, R ¹ is 2-(cyano(cyclopropyl)methoxy)ethyl. In some embodiments, R ¹ is butyl. In some embodiments, R ¹ is propyl. In some embodiments, R ¹ is (1-hydroxycyclobutyl)methyl. In some embodiments, R ¹ is 2-cyclopropoxyethyl. In some embodiments, R ¹ is 2-fluoro-2-methylpropyl. In some embodiments, R ¹ is methyl. In some embodiments, R ¹ is methyl-d3. In some embodiments, R ¹ is 2,2-difluoropropyl. In some embodiments, R ¹ is 2,2,2-trifluoroethyl. In some embodiments, R ¹ is 3,3,3-trifluoropropyl. In some embodiments, R ¹ is cyclopropyl. In some embodiments, R ¹ is (1- fluorocyclopropyl)methyl. In some embodiments, R ¹ is 2-hydroxypropyl. In some embodiments, R ¹ is ethyl. In some embodiments, R ¹ is ethyl-d5. In some embodiments, R ¹ is isopropyl. In some embodiments, R ¹ is 2-methoxyethyl. In some embodiments, R ¹ is (cyclopropyl)methyl. In some embodiments, R ¹ is (cyclopropyl)methyl-d ₂ . In some embodiments, R ¹ is 3-fluoropropyl. In some embodiments, R ¹ is 2-fluoroethyl. In some embodiments, R ¹ is 2-((2-cyanopropan-2-yl)oxy)ethyl. In some embodiments, R ¹ is 1,1,1-trifluoropropan-2-yl. In some embodiments, R ¹ is 2,2-difluoroethyl. In some embodiments, R ¹ is oxetan-3-yl. In some embodiments, R ¹ is oxetan-3-ylmethyl. In some embodiments, R ¹ is (oxetan-2-yl)methyl. In some embodiments, R ¹ is 3,3,3-trifluoro-2- hydroxypropyl. In some embodiments, R ¹ is 4,4,4-trifluorobutyl. In some embodiments, R ¹ is 3- methoxypropyl. In some embodiments, R ¹ is (3,3-difluorocyclobutyl)methyl. In some embodiments, R ¹ is (1-(difluoromethyl)cyclopropyl)methyl. In some embodiments, R ¹ is 5,5,5-trifluoropentyl. In some embodiments, R ¹ is (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl. In some embodiments, R ¹ is fluoromethyl. In some embodiments, R ¹ is (2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is 2-(trifluoromethoxy)ethyl. In some embodiments, R ¹ is neopentyl. In some embodiments, R ¹ is (1-methylcyclobutyl)methyl. In some embodiments, R ¹ is (2-methylcyclopropyl)methyl. In some embodiments, R ¹ is (2,2-difluorocyclopentyl)methyl. In some embodiments, R ¹ is 3-fluorocyclobut-2- en-1-yl. In some embodiments, R ¹ is 2-oxaspiro[3.3]heptan-6-yl. In some embodiments, R ¹ is 3- cyanocyclobutyl. In some embodiments, R ¹ is 3-fluorocyclobutyl. In some embodiments, R ¹ is 3,3- dimethylcyclobutyl. In some embodiments, R ¹ is spiro[3.3]heptan-2-yl. In some embodiments, R ¹ is 1-methylpyrrolidin-3-yl. In some embodiments, R ¹ is (3-methyloxetan-3-yl)methyl. In some embodiments, R ¹ is (1-methylcyclopropyl)methyl. In some embodiments, R ¹ is 1-methylcyclobutyl. In some embodiments, R ¹ is (2-fluorocyclopropyl)methyl. In some embodiments, R ¹ is (2,2-difluoro-3- methylcyclopropyl)methyl. In some embodiments, R ¹ is 1-cyclobutylethyl. In some embodiments, R ¹ is (2,2-dimethylcyclopropyl)methyl. In some embodiments, R ¹ is (3,3-difluorocyclopentyl)methyl. In some embodiments, R ¹ is 3-(trifluoromethyl)cyclobutyl. In some embodiments, R ¹ is 2-fluoropropyl. In some embodiments, R ¹ is 3-methoxycyclobutyl. In some embodiments, R ¹ is 3- (dimethylamino)cyclobutyl. In some embodiments, R ¹ is cyanomethyl. In some embodiments, R ¹ is (1-cyanocyclobutyl)methyl. In some embodiments, R ¹ is (1-cyanocyclopropyl)methyl. In some embodiments, R ¹ is 2-methoxypropyl. In some embodiments, R ¹ is (1- (methylsulfonyl)cyclopropyl)methyl. In some embodiments, R ¹ is 3-(methylsulfonyl)propyl. In some embodiments, R ¹ is 2-(methylsulfonyl)ethyl. In some embodiments, R ¹ is 3,3-difluorocyclobutyl. In some embodiments, R ¹ is (2,2-difluorocyclobutyl)methyl. In some embodiments, R ¹ is (cuban-1- yl)methyl. In some embodiments, R ¹ is (bicyclo[1.1.1]pentan-1-yl)methyl. In some embodiments, R ¹ is (bicyclo[2.1.1]hexan-1-yl)methyl. In some embodiments, R ¹ is (1,1-dimethylsilolan-3-yl)methyl. In some embodiments, R ¹ is (3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)methyl. In some embodiments, R ¹ is (2-oxabicyclo[2.1.1]hexan-1-yl)methyl. In some embodiments, R ¹ is (2- oxabicyclo[2.1.1]hexan-4-yl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (1-(cyanomethyl)cyclopropyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2-(cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2- cyclopropoxyethyl, 2-fluoro-2-methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3- trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, 2-hydroxypropyl, ethyl, isopropyl, 2- methoxyethyl, (cyclopropyl)methyl, 3-fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, (oxetan-2-yl)methyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3- fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, (2,2-difluorocyclopropyl)methyl, 2- (trifluoromethoxy)ethyl, neopentyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2- difluorocyclopentyl)methyl, 3-fluorocyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, 3- cyanocyclobutyl, 3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (3-methyloxetan- 3-yl)methyl, (1-methylcyclopropyl)methyl, 1-methylcyclobutyl, (2-fluorocyclopropyl)methyl, (2,2- difluoro-3-methylcyclopropyl)methyl, 1-cyclobutylethyl, (2,2-dimethylcyclopropyl)methyl, (3,3- difluorocyclopentyl)methyl, 3-(trifluoromethyl)cyclobutyl, 2-fluoropropyl, 3-methoxycyclobutyl, cyanomethyl, (1-cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, 2-methoxypropyl, 3,3- difluorocyclobutyl, and (2,2-difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (1-(cyanomethyl)cyclopropyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2-(cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2- cyclopropoxyethyl, 2-fluoro-2-methylpropyl, methyl, methyl-d3, 2,2-difluoropropyl, 2,2,2- trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, (R)-2-hydroxypropyl, ethyl, ethyl-d5, isopropyl, 2-methoxyethyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, 3- fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, ((R)-oxetan-2-yl)methyl, (S)-3,3,3-trifluoro-2- hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, ((S)-2,2-difluorocyclopropyl)methyl, ((R)-2,2-difluorocyclopropyl)methyl, 2- (trifluoromethoxy)ethyl, neopentyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2- difluorocyclopentyl)methyl, 3-fluorocyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, (1R,3r)-3- cyanocyclobutyl, (1r,3R)-3-fluorocyclobutyl, (1s,3S)-3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, 1-methylpyrrolidin-3-yl, (3-methyloxetan-3-yl)methyl, (1- methylcyclopropyl)methyl, 1-methylcyclobutyl, ((1R,2S)-2-fluorocyclopropyl)methyl, ((1S,2R)-2- fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3-methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro- 3-methylcyclopropyl)methyl, (S)-1-cyclobutylethyl, (R)-1-cyclobutylethyl, ((1S,2S)-2- fluorocyclopropyl)methyl, ((1R,2R)-2-fluorocyclopropyl)methyl, ((S)-2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1s,3S)-3-(trifluoromethyl)cyclobutyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, (1s,3S)-3-methoxycyclobutyl, (1s,3S)-3- (dimethylamino)cyclobutyl, cyanomethyl, (1-cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, (R)-3,3,3-trifluoro-2-hydroxypropyl, (S)-2-hydroxypropyl, (R)-2-methoxypropyl, (S)-2- methoxypropyl, (1-(methylsulfonyl)cyclopropyl)methyl, 3-(methylsulfonyl)propyl, 2- (methylsulfonyl)ethyl, 3,3-difluorocyclobutyl, (2,2-difluorocyclobutyl)methyl, (1S,3s)-3- cyanocyclobutyl, (1r,3R)-3-(trifluoromethyl)cyclobutyl, (1r,3R)-3-methoxycyclobutyl, (1r,3R)-3- (dimethylamino)cyclobutyl, (cuban-1-yl)methyl, (bicyclo[1.1.1]pentan-1-yl)methyl, (bicyclo[2.1.1]hexan-1-yl)methyl, (1,1-dimethylsilolan-3-yl)methyl, (3- (trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)methyl, (2-oxabicyclo[2.1.1]hexan-1-yl)methyl, and (2- oxabicyclo[2.1.1]hexan-4-yl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (1-(cyanomethyl)cyclopropyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2-(cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2- cyclopropoxyethyl, 2-fluoro-2-methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3- trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, (R)-2-hydroxypropyl, ethyl, isopropyl, 2- methoxyethyl, (cyclopropyl)methyl, 3-fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, ((R)-oxetan-2- yl)methyl, (S)-3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3- fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, ((S)-2,2-difluorocyclopropyl)methyl, ((R)-2,2- difluorocyclopropyl)methyl, 2-(trifluoromethoxy)ethyl, neopentyl, (1-methylcyclobutyl)methyl, (2- methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, 3-fluorocyclobut-2-en-1-yl, 2- oxaspiro[3.3]heptan-6-yl, (1R,3r)-3-cyanocyclobutyl, (1r,3R)-3-fluorocyclobutyl, (1s,3S)-3- fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, 1-methylpyrrolidin-3-yl, (3- methyloxetan-3-yl)methyl, (1-methylcyclopropyl)methyl, 1-methylcyclobutyl, ((1R,2S)-2- fluorocyclopropyl)methyl, ((1S,2R)-2-fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3- methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro-3-methylcyclopropyl)methyl, (S)-1-cyclobutylethyl, (R)-1-cyclobutylethyl, ((1S,2S)-2-fluorocyclopropyl)methyl, ((1R,2R)-2-fluorocyclopropyl)methyl, ((S)-2,2-dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1s,3S)-3- (trifluoromethyl)cyclobutyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, (1s,3S)-3-methoxycyclobutyl, (1s,3S)-3-(dimethylamino)cyclobutyl, cyanomethyl, (1-cyanocyclobutyl)methyl, (1- cyanocyclopropyl)methyl, (R)-3,3,3-trifluoro-2-hydroxypropyl, (S)-2-hydroxypropyl, (R)-2- methoxypropyl, (S)-2-methoxypropyl, (1-(methylsulfonyl)cyclopropyl)methyl, 3- (methylsulfonyl)propyl, 2-(methylsulfonyl)ethyl, 3,3-difluorocyclobutyl, (2,2- difluorocyclobutyl)methyl, (1S,3s)-3-cyanocyclobutyl, (1r,3R)-3-(trifluoromethyl)cyclobutyl, (1r,3R)- 3-methoxycyclobutyl, and (1r,3R)-3-(dimethylamino)cyclobutyl. It is understood that the stereochemistry for the R ¹ groups provided herein are assigned based on the R ¹ group being bonded to the oxygen as shown in the formulae provided herein (e.g., Formula (Ia), Formula (Ic), Formula (Ie), Formula (Ig), Formula (Ii), and Formula (Ik)). In some embodiments, R ¹ is (R)-2-hydroxypropyl. In some embodiments, R ¹ is ((R)-oxetan-2- yl)methyl. In some embodiments, R ¹ is (S)-3,3,3-trifluoro-2-hydroxypropyl. In some embodiments, R ¹ is ((S)-2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is ((R)-2,2- difluorocyclopropyl)methyl. In some embodiments, R ¹ is (1R,3r)-3-cyanocyclobutyl. In some embodiments, R ¹ is (1r,3R)-3-fluorocyclobutyl. In some embodiments, R ¹ is (1s,3S)-3- fluorocyclobutyl. In some embodiments, R ¹ is ((1R,2S)-2-fluorocyclopropyl)methyl. In some embodiments, R ¹ is ((1S,2R)-2-fluorocyclopropyl)methyl. In some embodiments, R ¹ is ((1S,3R)-2,2- difluoro-3-methylcyclopropyl)methyl. In some embodiments, R ¹ is ((1R,3S)-2,2-difluoro-3- methylcyclopropyl)methyl. In some embodiments, R ¹ is (S)-1-cyclobutylethyl. In some embodiments, R ¹ is (R)-1-cyclobutylethyl. In some embodiments, R ¹ is ((1S,2S)-2-fluorocyclopropyl)methyl. In some embodiments, R ¹ is ((1R,2R)-2-fluorocyclopropyl)methyl. In some embodiments, R ¹ is ((S)-2,2- dimethylcyclopropyl)methyl. In some embodiments, R ¹ is (1s,3S)-3-(trifluoromethyl)cyclobutyl. In some embodiments, R ¹ is (R)-2-fluoropropyl. In some embodiments, R ¹ is (S)-2-fluoropropyl. In some embodiments, R ¹ is (1s,3S)-3-methoxycyclobutyl. In some embodiments, R ¹ is (1s,3S)-3- (dimethylamino)cyclobutyl. In some embodiments, R ¹ is (R)-3,3,3-trifluoro-2-hydroxypropyl. In some embodiments, R ¹ is (S)-2-hydroxypropyl. In some embodiments, R ¹ is (R)-2-methoxypropyl. In some embodiments, R ¹ is (S)-2-methoxypropyl. In some embodiments, R ¹ is (1S,3s)-3-cyanocyclobutyl. In some embodiments, R ¹ is (1r,3R)-3-(trifluoromethyl)cyclobutyl. In some embodiments, R ¹ is (1r,3R)- 3-methoxycyclobutyl. In some embodiments, R ¹ is (1r,3R)-3-(dimethylamino)cyclobutyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (1-(cyanomethyl)cyclopropyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2-(cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2- cyclopropoxyethyl, 2-fluoro-2-methylpropyl, methyl, methyl-d3, 2,2-difluoropropyl, 2,2,2- trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, (R)-2-hydroxypropyl, ethyl, ethyl-d5, isopropyl, 2-methoxyethyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, 3- fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, ((R)-oxetan-2-yl)methyl, (S)-3,3,3-trifluoro-2- hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, ((S)-2,2-difluorocyclopropyl)methyl, ((R)-2,2-difluorocyclopropyl)methyl, 2- (trifluoromethoxy)ethyl, neopentyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2- difluorocyclopentyl)methyl, 3-fluorocyclobut-2-en-1-yl, 2-oxaspiro[3.3]heptan-6-yl, (1R,3r)-3- cyanocyclobutyl, (1r,3R)-3-fluorocyclobutyl, (1s,3S)-3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (3-methyloxetan-3-yl)methyl, (1-methylcyclopropyl)methyl, 1- methylcyclobutyl, ((1R,2S)-2-fluorocyclopropyl)methyl, ((1S,2R)-2-fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3-methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro-3- methylcyclopropyl)methyl, (S)-1-cyclobutylethyl, (R)-1-cyclobutylethyl, ((1S,2S)-2- fluorocyclopropyl)methyl, ((1R,2R)-2-fluorocyclopropyl)methyl, ((S)-2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1s,3S)-3-(trifluoromethyl)cyclobutyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, (1s,3S)-3-methoxycyclobutyl, cyanomethyl, (1- cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, (R)-3,3,3-trifluoro-2-hydroxypropyl, (S)-2- hydroxypropyl, (R)-2-methoxypropyl, (S)-2-methoxypropyl, 3,3-difluorocyclobutyl, (2,2- difluorocyclobutyl)methyl, (1S,3s)-3-cyanocyclobutyl, (1r,3R)-3-(trifluoromethyl)cyclobutyl, (1r,3R)- 3-methoxycyclobutyl, (cuban-1-yl)methyl, (bicyclo[1.1.1]pentan-1-yl)methyl, (bicyclo[2.1.1]hexan-1- yl)methyl, (1,1-dimethylsilolan-3-yl)methyl, (3-(trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)methyl, (2- oxabicyclo[2.1.1]hexan-1-yl)methyl, and (2-oxabicyclo[2.1.1]hexan-4-yl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, (1-(cyanomethyl)cyclopropyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2-(cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2- cyclopropoxyethyl, 2-fluoro-2-methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3- trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, (R)-2-hydroxypropyl, ethyl, isopropyl, 2- methoxyethyl, (cyclopropyl)methyl, 3-fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, ((R)-oxetan-2- yl)methyl, (S)-3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3- fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, ((S)-2,2-difluorocyclopropyl)methyl, ((R)-2,2- difluorocyclopropyl)methyl, 2-(trifluoromethoxy)ethyl, neopentyl, (1-methylcyclobutyl)methyl, (2- methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, 3-fluorocyclobut-2-en-1-yl, 2- oxaspiro[3.3]heptan-6-yl, (1R,3r)-3-cyanocyclobutyl, (1r,3R)-3-fluorocyclobutyl, (1s,3S)-3- fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (3-methyloxetan-3-yl)methyl, (1- methylcyclopropyl)methyl, 1-methylcyclobutyl, ((1R,2S)-2-fluorocyclopropyl)methyl, ((1S,2R)-2- fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3-methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro- 3-methylcyclopropyl)methyl, (S)-1-cyclobutylethyl, (R)-1-cyclobutylethyl, ((1S,2S)-2- fluorocyclopropyl)methyl, ((1R,2R)-2-fluorocyclopropyl)methyl, ((S)-2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1s,3S)-3-(trifluoromethyl)cyclobutyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, (1s,3S)-3-methoxycyclobutyl, cyanomethyl, (1- cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, (R)-3,3,3-trifluoro-2-hydroxypropyl, (S)-2- hydroxypropyl, (R)-2-methoxypropyl, (S)-2-methoxypropyl, 3,3-difluorocyclobutyl, (2,2- difluorocyclobutyl)methyl, (1S,3s)-3-cyanocyclobutyl, (1r,3R)-3-(trifluoromethyl)cyclobutyl, and (1r,3R)-3-methoxycyclobutyl. In some embodiments, R ¹ is C3-C7-cycloalkyl-C1-C4-alkylene. In some embodiments, R ¹ is C3-C7-cycloalkyl-C1-C4-alkylene optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C ₁ -C ₄ -alkylsulfonyl, C ₃ -C ₆ -cycloalkyl, hydroxyl, C ₁ -C ₄ -alkoxy, and C ₂ -C ₄ -dialkylamino. In some embodiments, R ¹ is C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, hydroxyl, C1-C4-haloalkyl, C1-C4- alkyl, cyano, and C ₁ -C ₄ -alkylsulfonyl. In some embodiments, R ¹ is C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene optionally substituted with one or more substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, hydroxyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ - alkyl, and cyano. In some embodiments, R ¹ is C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene optionally substituted with one, two, or three substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, hydroxyl, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkyl, and cyano. In some embodiments, R ¹ is C ₃ -C ₅ -cycloalkyl-C ₁ -C ₂ -alkylene optionally substituted with one, two, or three substituents selected from: cyanomethyl, halogen, hydroxyl, C ₁ -haloalkyl, methyl, cyano, and methylsulfonyl. In some embodiments, R ¹ is C ₃ -C ₅ -cycloalkyl-C ₁ -C ₂ -alkylene optionally substituted with one, two, or three substituents selected from: cyanomethyl, halogen, hydroxyl, C ₁ -haloalkyl, methyl, and cyano. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, and (cyclobutyl)ethyl; wherein each group is optionally substituted with one, two, or three substituents selected from: cyano, cyanomethyl, difluoromethyl, fluoro, hydroxyl, methyl, and methylsulfonyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (cyclopropyl)methyl, and (cyclobutyl)ethyl; wherein each group is optionally substituted with one, two, or three substituents selected from: cyano, cyanomethyl, difluoromethyl, fluoro, hydroxyl, methyl, and methylsulfonyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, and (cyclobutyl)ethyl; wherein each group is optionally substituted with one, two, or three substituents selected from: cyano, cyanomethyl, difluoromethyl, fluoro, hydroxyl, and methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (cyclopropyl)methyl, and (cyclobutyl)ethyl; wherein each group is optionally substituted with one, two, or three substituents selected from: cyano, cyanomethyl, difluoromethyl, fluoro, hydroxyl, and methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (1- (cyanomethyl)cyclopropyl)methyl, (1-fluorocyclobutyl)methyl, (1-hydroxycyclobutyl)methyl, (1- fluorocyclopropyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, (2,2-difluorocyclopropyl)methyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, (1- methylcyclopropyl)methyl, (2-fluorocyclopropyl)methyl, (2,2-difluoro-3-methylcyclopropyl)methyl, 1-cyclobutylethyl, (2,2-dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1- cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, (1-(methylsulfonyl)cyclopropyl)methyl, and (2,2-difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (1- (cyanomethyl)cyclopropyl)methyl, (1-fluorocyclobutyl)methyl, (1-hydroxycyclobutyl)methyl, (1- fluorocyclopropyl)methyl, (cyclopropyl)methyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, (2,2-difluorocyclopropyl)methyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, (1-methylcyclopropyl)methyl, (2- fluorocyclopropyl)methyl, (2,2-difluoro-3-methylcyclopropyl)methyl, 1-cyclobutylethyl, (2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1-cyanocyclobutyl)methyl, (1- cyanocyclopropyl)methyl, (1-(methylsulfonyl)cyclopropyl)methyl, and (2,2- difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (1- (cyanomethyl)cyclopropyl)methyl, (1-fluorocyclobutyl)methyl, (1-hydroxycyclobutyl)methyl, (1- fluorocyclopropyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, (2,2-difluorocyclopropyl)methyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, (1- methylcyclopropyl)methyl, (2-fluorocyclopropyl)methyl, (2,2-difluoro-3-methylcyclopropyl)methyl, 1-cyclobutylethyl, (2,2-dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1- cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, and (2,2-difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (1- (cyanomethyl)cyclopropyl)methyl, (1-fluorocyclobutyl)methyl, (1-hydroxycyclobutyl)methyl, (1- fluorocyclopropyl)methyl, (cyclopropyl)methyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, (2,2-difluorocyclopropyl)methyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, (1-methylcyclopropyl)methyl, (2- fluorocyclopropyl)methyl, (2,2-difluoro-3-methylcyclopropyl)methyl, 1-cyclobutylethyl, (2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1-cyanocyclobutyl)methyl, (1- cyanocyclopropyl)methyl, and (2,2-difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (1- (cyanomethyl)cyclopropyl)methyl, (1-fluorocyclobutyl)methyl, (1-hydroxycyclobutyl)methyl, (1- fluorocyclopropyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, ((S)-2,2- difluorocyclopropyl)methyl, ((R)-2,2-difluorocyclopropyl)methyl, (1-methylcyclobutyl)methyl, (2- methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, (1-methylcyclopropyl)methyl, ((1R,2S)- 2-fluorocyclopropyl)methyl, ((1S,2R)-2-fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3- methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro-3-methylcyclopropyl)methyl, (S)-1-cyclobutylethyl, (R)-1-cyclobutylethyl, ((1S,2S)-2-fluorocyclopropyl)methyl, ((1R,2R)-2-fluorocyclopropyl)methyl, ((S)-2,2-dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1-cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, (1-(methylsulfonyl)cyclopropyl)methyl, and (2,2- difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (1- (cyanomethyl)cyclopropyl)methyl, (1-fluorocyclobutyl)methyl, (1-hydroxycyclobutyl)methyl, (1- fluorocyclopropyl)methyl, (cyclopropyl)methyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, ((S)-2,2-difluorocyclopropyl)methyl, ((R)-2,2- difluorocyclopropyl)methyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2- difluorocyclopentyl)methyl, (1-methylcyclopropyl)methyl, ((1R,2S)-2-fluorocyclopropyl)methyl, ((1S,2R)-2-fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3-methylcyclopropyl)methyl, ((1R,3S)- 2,2-difluoro-3-methylcyclopropyl)methyl, (S)-1-cyclobutylethyl, (R)-1-cyclobutylethyl, ((1S,2S)-2- fluorocyclopropyl)methyl, ((1R,2R)-2-fluorocyclopropyl)methyl, ((S)-2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1-cyanocyclobutyl)methyl, (1- cyanocyclopropyl)methyl, (1-(methylsulfonyl)cyclopropyl)methyl, and (2,2- difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (1- (cyanomethyl)cyclopropyl)methyl, (1-fluorocyclobutyl)methyl, (1-hydroxycyclobutyl)methyl, (1- fluorocyclopropyl)methyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, ((S)-2,2- difluorocyclopropyl)methyl, ((R)-2,2-difluorocyclopropyl)methyl, (1-methylcyclobutyl)methyl, (2- methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, (1-methylcyclopropyl)methyl, ((1R,2S)- 2-fluorocyclopropyl)methyl, ((1S,2R)-2-fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3- methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro-3-methylcyclopropyl)methyl, (S)-1-cyclobutylethyl, (R)-1-cyclobutylethyl, ((1S,2S)-2-fluorocyclopropyl)methyl, ((1R,2R)-2-fluorocyclopropyl)methyl, ((S)-2,2-dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1-cyanocyclobutyl)methyl, (1-cyanocyclopropyl)methyl, and (2,2-difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, (cyclobutyl)methyl, (1- (cyanomethyl)cyclopropyl)methyl, (1-fluorocyclobutyl)methyl, (1-hydroxycyclobutyl)methyl, (1- fluorocyclopropyl)methyl, (cyclopropyl)methyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, ((S)-2,2-difluorocyclopropyl)methyl, ((R)-2,2- difluorocyclopropyl)methyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2- difluorocyclopentyl)methyl, (1-methylcyclopropyl)methyl, ((1R,2S)-2-fluorocyclopropyl)methyl, ((1S,2R)-2-fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3-methylcyclopropyl)methyl, ((1R,3S)- 2,2-difluoro-3-methylcyclopropyl)methyl, (S)-1-cyclobutylethyl, (R)-1-cyclobutylethyl, ((1S,2S)-2- fluorocyclopropyl)methyl, ((1R,2R)-2-fluorocyclopropyl)methyl, ((S)-2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1-cyanocyclobutyl)methyl, (1- cyanocyclopropyl)methyl, and (2,2-difluorocyclobutyl)methyl. In some embodiments, R ¹ is selected from: (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , (3,3-difluorocyclobutyl)methyl, ((S)-2,2-difluorocyclopropyl)methyl, and ((R)-2,2- difluorocyclopropyl)methyl. In some embodiments, R ¹ is selected from: (cyclopropyl)methyl, (3,3- difluorocyclobutyl)methyl, ((S)-2,2-difluorocyclopropyl)methyl, and ((R)-2,2- difluorocyclopropyl)methyl. In some embodiments, R ¹ is C ₁ -C ₆ -alkyl. In some embodiments, R ¹ is C ₁ -C ₆ -alkyl optionally substituted with one or more substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, cyano, C ₁ -C ₄ - alkylsulfonyl, C ₃ -C ₆ -cycloalkyl, hydroxyl, C ₁ -C ₄ -alkoxy, and C ₂ -C ₄ -dialkylamino. In some embodiments, R ¹ is C ₁ -C ₆ -alkyl optionally substituted with one or more substituents selected from: halogen, hydroxyl, cyano, C ₁ -C ₄ -alkoxy, and C ₁ -C ₄ -alkylsulfonyl. In some embodiments, R ¹ is C ₁ -C ₆ -alkyl optionally substituted with one or more substituents selected from: halogen, hydroxyl, cyano, and C ₁ -C ₄ -alkoxy. In some embodiments, R ¹ is C1-C6-alkyl optionally substituted with one, two, three, or four substituents selected from: halogen, hydroxyl, cyano, and C1-C4-alkoxy. In some embodiments, R ¹ is C1-C5-alkyl optionally substituted with one, two, three, or four substituents selected from: halogen, hydroxyl, cyano, methoxy, and methylsulfonyl. In some embodiments, R ¹ is C1-C5-alkyl optionally substituted with one, two, three, or four substituents selected from: halogen, hydroxyl, cyano, and methoxy. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, methyl, methyl- d3, ethyl, ethyl-d5, isopropyl, pentyl, and neopentyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: fluoro, hydroxyl, cyano, methoxy, and methylsulfonyl. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, methyl, ethyl, isopropyl, pentyl, and neopentyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: fluoro, hydroxyl, cyano, methoxy, and methylsulfonyl. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, methyl, methyl- d3, ethyl, ethyl-d5, isopropyl, pentyl, and neopentyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: fluoro, hydroxyl, cyano, and methoxy. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, methyl, ethyl, isopropyl, pentyl, and neopentyl; wherein each group is optionally substituted with one, two, three, or four substituents selected from: fluoro, hydroxyl, cyano, and methoxy. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, 2-fluoro-2- methylpropyl, methyl, methyl-d3, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2- hydroxypropyl, ethyl, ethyl-d5, isopropyl, 3-fluoropropyl, 2-fluoroethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, fluoromethyl, neopentyl, 2-fluoropropyl, cyanomethyl, 2-methoxypropyl, 3-(methylsulfonyl)propyl, and 2-(methylsulfonyl)ethyl. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, 2-fluoro-2- methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2- hydroxypropyl, ethyl, isopropyl, 3-fluoropropyl, 2-fluoroethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, fluoromethyl, neopentyl, 2-fluoropropyl, cyanomethyl, 2-methoxypropyl, 3-(methylsulfonyl)propyl, and 2-(methylsulfonyl)ethyl. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, 2-fluoro-2- methylpropyl, methyl, methyl-d ₃ , 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2- hydroxypropyl, ethyl, ethyl-d ₅ , isopropyl, 3-fluoropropyl, 2-fluoroethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, fluoromethyl, neopentyl, 2-fluoropropyl, cyanomethyl, and 2-methoxypropyl. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, 2-fluoro-2- methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 2- hydroxypropyl, ethyl, isopropyl, 3-fluoropropyl, 2-fluoroethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, fluoromethyl, neopentyl, 2-fluoropropyl, cyanomethyl, and 2-methoxypropyl. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, 2-fluoro-2- methylpropyl, methyl, methyl-d3, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, (R)-2- hydroxypropyl, ethyl, ethyl-d5, isopropyl, 3-fluoropropyl, 2-fluoroethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, (S)-3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, fluoromethyl, neopentyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, cyanomethyl, (R)-3,3,3-trifluoro-2- hydroxypropyl, (S)-2-hydroxypropyl, (R)-2-methoxypropyl, (S)-2-methoxypropyl, 3- (methylsulfonyl)propyl, and 2-(methylsulfonyl)ethyl. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, 2-fluoro-2- methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, (R)-2- hydroxypropyl, ethyl, isopropyl, 3-fluoropropyl, 2-fluoroethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, (S)-3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, fluoromethyl, neopentyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, cyanomethyl, (R)-3,3,3-trifluoro-2- hydroxypropyl, (S)-2-hydroxypropyl, (R)-2-methoxypropyl, (S)-2-methoxypropyl, 3- (methylsulfonyl)propyl, and 2-(methylsulfonyl)ethyl. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, 2-fluoro-2- methylpropyl, methyl, methyl-d3, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, (R)-2- hydroxypropyl, ethyl, ethyl-d5, isopropyl, 3-fluoropropyl, 2-fluoroethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, (S)-3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, fluoromethyl, neopentyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, cyanomethyl, (R)-3,3,3-trifluoro-2- hydroxypropyl, (S)-2-hydroxypropyl, (R)-2-methoxypropyl, and (S)-2-methoxypropyl. In some embodiments, R ¹ is selected from: isobutyl, isopentyl, butyl, propyl, 2-fluoro-2- methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, (R)-2- hydroxypropyl, ethyl, isopropyl, 3-fluoropropyl, 2-fluoroethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, (S)-3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, fluoromethyl, neopentyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, cyanomethyl, (R)-3,3,3-trifluoro-2- hydroxypropyl, (S)-2-hydroxypropyl, (R)-2-methoxypropyl, and (S)-2-methoxypropyl. In some embodiments, R ¹ is selected from: 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, ethyl, and ethyl-d ₅ . In some embodiments, R ¹ is selected from: 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, and ethyl. In some embodiments, R ¹ is C ₃ -C ₇ -cycloalkyl. In some embodiments, R ¹ is C ₃ -C ₇ -cycloalkyl optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C1- C4-alkylsulfonyl, C3-C6-cycloalkyl, hydroxyl, C1-C4-alkoxy, and C2-C4-dialkylamino. In some embodiments, R ¹ is C3-C7-cycloalkyl optionally substituted with one or more substituents selected from: cyano, halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, and C2-C4- dialkylamino. In some embodiments, R ¹ is C3-C7-cycloalkyl optionally substituted with one or more substituents selected from: cyano, halogen, C1-C4-alkyl, C1-C4-haloalkyl, and C1-C4-alkoxy. In some embodiments, R ¹ is C3-C7-cycloalkyl optionally substituted with one or two substituents selected from: cyano, halogen, C1-C4-alkyl, C1-C4-haloalkyl, and C1-C4-alkoxy. In some embodiments, R ¹ is C3-C5-cycloalkyl optionally substituted with one or two substituents selected from: cyano, halogen, methyl, C1-haloalkyl, methoxy, and dimethylamino. In some embodiments, R ¹ is C3-C7-cycloalkyl optionally substituted with one or two substituents selected from: cyano, halogen, methyl, C1-haloalkyl, and methoxy. In some embodiments, R ¹ is selected from: cyclopentyl, cyclobutyl, and cyclopropyl; wherein each group is optionally substituted with one or two substituents selected from: cyano, fluoro, methyl, trifluoromethyl, methoxy, and dimethylamino. In some embodiments, R ¹ is selected from: cyclopentyl, cyclobutyl, and cyclopropyl; wherein each group is optionally substituted with one or two substituents selected from: cyano, fluoro, methyl, trifluoromethyl, and methoxy. In some embodiments, R ¹ is selected from: cyclopentyl, cyclobutyl, cyclopropyl, 3- cyanocyclobutyl, 3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, 1-methylcyclobutyl, 3- (trifluoromethyl)cyclobutyl, 3-methoxycyclobutyl, 3-(dimethylamino)cyclobutyl, and 3,3- difluorocyclobutyl. In some embodiments, R ¹ is selected from cyclopentyl, cyclobutyl, cyclopropyl, 3- cyanocyclobutyl, 3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, 1-methylcyclobutyl, 3- (trifluoromethyl)cyclobutyl, 3-methoxycyclobutyl, and 3,3-difluorocyclobutyl. In some embodiments, R ¹ is selected from: cyclopentyl, cyclobutyl, cyclopropyl, (1R,3r)-3- cyanocyclobutyl, (1r,3R)-3-fluorocyclobutyl, (1s,3S)-3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, 1- methylcyclobutyl, (1s,3S)-3-(trifluoromethyl)cyclobutyl, (1s,3S)-3-methoxycyclobutyl, (1s,3S)-3- (dimethylamino)cyclobutyl, 3,3-difluorocyclobutyl, (1S,3s)-3-cyanocyclobutyl, (1r,3R)-3- (trifluoromethyl)cyclobutyl, (1r,3R)-3-methoxycyclobutyl, and (1r,3R)-3-(dimethylamino)cyclobutyl. In some embodiments, R ¹ is selected from: cyclopentyl, cyclobutyl, cyclopropyl, (1R,3r)-3- cyanocyclobutyl, (1r,3R)-3-fluorocyclobutyl, (1s,3S)-3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, 1- methylcyclobutyl, (1s,3S)-3-(trifluoromethyl)cyclobutyl, (1s,3S)-3-methoxycyclobutyl, 3,3- difluorocyclobutyl, (1S,3s)-3-cyanocyclobutyl, (1r,3R)-3-(trifluoromethyl)cyclobutyl, and (1r,3R)-3- methoxycyclobutyl. In some embodiments, R ¹ is C ₁ -C ₄ -alkyl-O-C ₂ -C ₄ -alkylene. In some embodiments, R ¹ is C1-C4-alkyl-O-C2-C4-alkylene optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C1-C4-alkylsulfonyl, C3-C6-cycloalkyl, hydroxyl, C1-C4-alkoxy, and C2-C4-dialkylamino. In some embodiments, R ¹ is C1-C4-alkyl-O-C2-C4-alkylene optionally substituted with one or more substituents selected from: cyano, halogen, and C3-C6-cycloalkyl. In some embodiments, R ¹ is C1-C3-alkyl-O-C2-C3-alkylene optionally substituted with one or more substituents selected from: cyano, halogen, and cyclopropyl. In some embodiments, R ¹ is C1-C3-alkyl-O-C2-C3-alkylene optionally substituted with one, two, or three substituents selected from: cyano, halogen, and cyclopropyl. In some embodiments, R ¹ is selected from: methoxyethyl, ((propyl)oxy)ethyl, and methoxypropyl; wherein each group is optionally substituted with one, two, or three substituents selected from: cyano, fluoro, and cyclopropyl. In some embodiments, R ¹ is selected from: 2-(methoxy)ethyl, 2-methoxyethyl, 2-((propan-2- yl)oxy)ethyl, and 3-methoxypropyl; wherein each group is optionally substituted with one, two, or three substituents selected from: cyano, fluoro, and cyclopropyl. In some embodiments, R ¹ is selected from: 2-(cyano(cyclopropyl)methoxy)ethyl, 2- methoxyethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 3-methoxypropyl, and 2-(trifluoromethoxy)ethyl. In some embodiments, R ¹ is C3-C7-cycloalkyl-O-C2-C4-alkylene. In some embodiments, R ¹ is C3-C7-cycloalkyl-O-C2-C4-alkylene optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C1-C4-alkylsulfonyl, C3-C6-cycloalkyl, hydroxyl, C1-C4-alkoxy, and C2-C4-dialkylamino. In some embodiments, R ¹ is cyclopropoxyethyl. In some embodiments, R ¹ is 3-7-membered-heterocyclyl. In some embodiments, R ¹ is 3-7-membered-heterocyclyl optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C ₁ -C ₄ -alkylsulfonyl, C ₃ -C ₆ -cycloalkyl, hydroxyl, C ₁ -C ₄ -alkoxy, and C ₂ -C ₄ -dialkylamino. In some embodiments, R ¹ is 3-7-membered-heterocyclyl optionally substituted with one or more C ₁ -C ₄ -alkyl substituents. In some embodiments, R ¹ is 4-5-membered-heterocyclyl optionally substituted with one or more C ₁ -C ₄ -alkyl substituents. In some embodiments, R ¹ is 4-5-membered-heterocyclyl optionally substituted with one C ₁ - C ₄ -alkyl substituent. In some embodiments, R ¹ is 4-membered-heterocyclyl. In some embodiments, R ¹ is oxetan-3-yl or pyrrolidin-3-yl; wherein each group is optionally substituted with one methyl substituent. In some embodiments, R ¹ is oxetan-3-yl or 1-methylpyrrolidin-3-yl. In some embodiments, R ¹ is 3-7-membered-heterocyclyl-C1-C4-alkylene. In some embodiments, R ¹ is 3-7-membered-heterocyclyl-C1-C4-alkylene optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C1-C4-alkylsulfonyl, C3-C6-cycloalkyl, hydroxyl, C1-C4-alkoxy, and C2-C4- dialkylamino. In some embodiments, R ¹ is 3-7-membered-heterocyclyl-C1-C4-alkylene optionally substituted with one or more C1-C4-alkyl substituents. In some embodiments, R ¹ is (4-5-membered-heterocyclyl)CH2- optionally substituted with one or more methyl substituents. In some embodiments, R ¹ is (4-membered-heterocyclyl)CH2- optionally substituted with one or more methyl substituents. In some embodiments, R ¹ is (4-5-membered-heterocyclyl)CH2- optionally substituted with one methyl substituent. In some embodiments, R ¹ is (4-membered-heterocyclyl)CH2- optionally substituted with one methyl substituent. In some embodiments, R ¹ is (oxetanyl)methyl or (silolanyl)methyl; wherein each group is optionally substituted with one or two methyl substituents. In some embodiments, R ¹ is selected from (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, and (silolan-3-yl)methyl; wherein each group is optionally substituted with one or two methyl substituents. In some embodiments, R ¹ is (oxetan-3-yl)methyl or (oxetan-2-yl)methyl; wherein each group is optionally substituted with one methyl substituent. In some embodiments, R ¹ is selected from: (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, (3- methyloxetan-3-yl)methyl, and (1,1-dimethylsilolan-3-yl)methyl. In some embodiments, R ¹ is selected from: (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, and (3- methyloxetan-3-yl)methyl. In some embodiments, R ¹ is selected from: oxetan-3-ylmethyl, ((R)-oxetan-2-yl)methyl, (3- methyloxetan-3-yl)methyl, and (1,1-dimethylsilolan-3-yl)methyl. In some embodiments, R ¹ is selected from: oxetan-3-ylmethyl, ((R)-oxetan-2-yl)methyl, and (3-methyloxetan-3-yl)methyl. In some embodiments, R ¹ is C ₄ -C ₈ -bicycloalkyl-C ₁ -C ₄ -alkylene. In some embodiments, R ¹ is C ₄ -C ₈ -bicycloalkyl-C ₁ -C ₄ -alkylene optionally substituted with one or more substituents selected from: halogen and C ₁ -C ₄ -haloalkyl. In some embodiments, R ¹ is (C ₅ -C ₆ -bicycloalkyl)CH ₂ - optionally substituted with one or more substituents selected from: fluoro and trifluoromethyl. In some embodiments, R ¹ is (C ₅ -C ₆ -bicycloalkyl)CH ₂ - optionally substituted with one substituent selected from: fluoro and trifluoromethyl. In some embodiments, R ¹ is (bicyclo[1.1.1]pentanyl)methyl or (bicyclo[2.1.1]hexanyl)methyl; wherein each group is optionally substituted with one substituent selected from: fluoro and trifluoromethyl. In some embodiments, R ¹ is (bicyclo[1.1.1]pentan-1-yl)methyl or (bicyclo[2.1.1]hexan-1- yl)methyl; wherein each group is optionally substituted with one substituent selected from: fluoro and trifluoromethyl. In some embodiments, R ¹ is selected from: (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl, (bicyclo[1.1.1]pentan-1-yl)methyl, (bicyclo[2.1.1]hexan-1-yl)methyl, and (3- (trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)methyl. In some embodiments, R ¹ is C4-C8-bicycloalkyl-C1-C4-alkylene optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C1-C4-alkylsulfonyl, C3-C6-cycloalkyl, hydroxyl, C1-C4-alkoxy, and C2-C4-dialkylamino. In some embodiments, R ¹ is C4-C8-bicycloalkyl-C1-C4-alkylene optionally substituted with one or more halogen substituents. In some embodiments, R ¹ is (C5-bicycloalkyl)CH2- optionally substituted with one or more fluoro substituents. In some embodiments, R ¹ is (C5-bicycloalkyl)CH2- optionally substituted with one fluoro substituent. In some embodiments, R ¹ is (bicyclo[1.1.1]pentanyl)methyl optionally substituted with one fluoro substituent. In some embodiments, R ¹ is (bicyclo[1.1.1]pentan-1-yl)methyl optionally substituted with one fluoro substituent. In some embodiments, R ¹ is C ₄ -C ₇ -cycloalkenyl. In some embodiments, R ¹ is C4-C7-cycloalkenyl optionally substituted with one or more substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, cyano, C ₁ - C ₄ -alkylsulfonyl, C ₃ -C ₆ -cycloalkyl, hydroxyl, C ₁ -C ₄ -alkoxy, and C ₂ -C ₄ -dialkylamino. In some embodiments, R ¹ is C ₄ -C ₇ -cycloalkenyl optionally substituted with one or more halogen substituents. In some embodiments, R ¹ is C ₄ -cycloalkenyl optionally substituted with one halogen substituent. In some embodiments, R ¹ is cyclobutenyl optionally substituted with one fluoro substituent. In some embodiments, R ¹ is cyclobut-2-en-1-yl optionally substituted with one fluoro substituent. In some embodiments, R ¹ is 5-11-membered-spiro-heterocyclyl. In some embodiments, R ¹ is 5-11-membered-spiro-heterocyclyl optionally substituted with one or more substituents selected from: cyano-C ₁ -C ₄ -alkylene, halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, cyano, C1-C4-alkylsulfonyl, C3-C6-cycloalkyl, hydroxyl, C1-C4-alkoxy, and C2-C4-dialkylamino. In some embodiments, R ¹ is 5-11-membered-spiro-heterocyclyl. In some embodiments, R ¹ is 7-membered-spiro-heterocyclyl. In some embodiments, R ¹ is oxaspiro[3.3]heptanyl. In some embodiments, R ¹ is C5-C11-spiro-cycloalkyl. In some embodiments, R ¹ is C5-C11-spiro-cycloalkyl optionally substituted with one or more substituents selected from: cyano-C1-C4-alkylene, halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C1- C4-alkylsulfonyl, C3-C6-cycloalkyl, hydroxyl, C1-C4-alkoxy, and C2-C4-dialkylamino. In some embodiments, R ¹ is C5-C11-spiro-cycloalkyl. In some embodiments, R ¹ is C7-spiro-cycloalkyl. In some embodiments, R ¹ is spiro[3.3]heptanyl. In some embodiments, R ¹ is cubanyl-C1-C4-alkylene. In some embodiments, R ¹ is (cuban-1-yl)methyl. In some embodiments, R ¹ is 4-8-membered-heterobicyclyl-C1-C4-alkylene. In some embodiments, R ¹ is 6-membered-heterobicyclyl-CH2-. In some embodiments, R ¹ is (2-oxabicyclo[2.1.1]hexanyl)methyl. In some embodiments, R ¹ is (2-oxabicyclo[2.1.1]hexan-1-yl)methyl or (2- oxabicyclo[2.1.1]hexan-4-yl)methyl. One aspect of the present disclosure encompasses, inter alia, a compound of (Ie): or a pharmaceutically acceptable salt thereof, wherein: R ¹ is selected from: C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene, C ₁ -C ₆ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₁ -C ₄ - alkyl-O-C ₂ -C ₄ -alkylene, 3-7-membered-heterocyclyl-C ₁ -C ₄ -alkylene, C ₄ -C ₈ -bicycloalkyl-C ₁ -C ₄ - alkylene, C ₅ -C ₁₁ -spiro-cycloalkyl, and cubanyl-C ₁ -C ₄ -alkylene; wherein each R ¹ group is optionally substituted with one or more substituents selected from: halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -haloalkyl, cyano, C ₃ -C ₆ -cycloalkyl, and hydroxyl. One embodiment pertains to a compound of Formula (Ie): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ is selected from: C ₃ -C ₇ -cycloalkyl-C ₁ -C ₄ -alkylene, C ₁ -C ₆ -alkyl, C ₃ -C ₇ -cycloalkyl, C ₁ -C ₄ - alkyl-O-C ₂ -C ₄ -alkylene, 3-7-membered-heterocyclyl-C ₁ -C ₄ -alkylene, C ₄ -C ₈ -bicycloalkyl-C ₁ -C ₄ - alkylene, and C ₅ -C ₁₁ -spiro-cycloalkyl; wherein each R ¹ group is optionally substituted with one or more substituents selected from: halogen, C1-C4-alkyl, C1-C4-haloalkyl, cyano, C3-C6-cycloalkyl, and hydroxyl. In some embodiments, R ¹ is selected from: R ¹ is selected from: (C3-C5-cycloalkyl)CD2-, (C3- C5-cycloalkyl)CH2-, C1-C5-alkyl, C3-C5-cycloalkyl, C1-C3-alkyl-O-C2-C3-alkylene, (4-membered- heterocyclyl)CH2-, (C5-C6-bicycloalkyl)CH2-, C7-spiro-cycloalkyl, and (cubanyl)CH2-; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, methyl, difluoromethyl, trifluoromethyl, cyano, cyclopropyl, and hydroxyl. In some embodiments, R ¹ is selected from: R ¹ is selected from: (C3-C5-cycloalkyl)CH2-, C1- C5-alkyl, C3-C5-cycloalkyl, C1-C3-alkyl-O-C2-C3-alkylene, (4-membered-heterocyclyl)CH2-, (C5- bicycloalkyl)CH2-, and C7-spiro-cycloalkyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, methyl, difluoromethyl, trifluoromethyl, cyano, cyclopropyl, and hydroxyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, methyl, ethyl, ethyl-d5, cyclopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, isopropyl, ((propyl)oxy)ethyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, spiro[3.3]heptanyl, (cubanyl)methyl, and (bicyclo[2.1.1]hexanyl)methyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, methyl, difluoromethyl, trifluoromethyl, cyano, cyclopropyl, and hydroxyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, cyclobutyl, methoxyethyl, butyl, propyl, methyl, ethyl, cyclopropyl, (cyclopropyl)methyl, isopropyl, ((propyl)oxy)ethyl, (oxetanyl)methyl, methoxypropyl, pentyl, (bicyclo[1.1.1]pentanyl)methyl, and spiro[3.3]heptanyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, methyl, difluoromethyl, trifluoromethyl, cyano, cyclopropyl, and hydroxyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, cyclobutyl, 2-methoxyethyl, butyl, propyl, methyl, ethyl, ethyl-d ₅ , cyclopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, isopropyl, 2-((propan-2-yl)oxy)ethyl, (oxetan-2-yl)methyl, 3-methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1-yl)methyl, 2-(methoxy)ethyl, spiro[3.3]heptan-2-yl, (cuban-1-yl)methyl, and (bicyclo[2.1.1]hexan-1-yl)methyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, methyl, difluoromethyl, trifluoromethyl, cyano, cyclopropyl, and hydroxyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, cyclobutyl, 2-methoxyethyl, butyl, propyl, methyl, ethyl, cyclopropyl, (cyclopropyl)methyl, isopropyl, 2-((propan-2-yl)oxy)ethyl, (oxetan-2-yl)methyl, 3-methoxypropyl, pentyl, (bicyclo[1.1.1]pentan-1-yl)methyl, 2-(methoxy)ethyl, and spiro[3.3]heptan-2-yl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, methyl, difluoromethyl, trifluoromethyl, cyano, cyclopropyl, and hydroxyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2- (cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2-fluoro-2- methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1- fluorocyclopropyl)methyl, ethyl, ethyl-d5, isopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, 3- fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 2,2-difluoroethyl, (oxetan-2- yl)methyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3- fluorobicyclo[1.1.1]pentan-1-yl)methyl, (2,2-difluorocyclopropyl)methyl, 2-(trifluoromethoxy)ethyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, 3- fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (1-methylcyclopropyl)methyl, 1- methylcyclobutyl, (2-fluorocyclopropyl)methyl, (2,2-difluoro-3-methylcyclopropyl)methyl, (2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, 3-(trifluoromethyl)cyclobutyl, 2- fluoropropyl, (cuban-1-yl)methyl, (bicyclo[1.1.1]pentan-1-yl)methyl, and (bicyclo[2.1.1]hexan-1- yl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2- (cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2-fluoro-2- methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1- fluorocyclopropyl)methyl, ethyl, isopropyl, (cyclopropyl)methyl, 3-fluoropropyl, 2-fluoroethyl, 2-((2- cyanopropan-2-yl)oxy)ethyl, 2,2-difluoroethyl, (oxetan-2-yl)methyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl, (2,2-difluorocyclopropyl)methyl, 2-(trifluoromethoxy)ethyl, (1-methylcyclobutyl)methyl, (2- methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, 3-fluorocyclobutyl, 3,3- dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (1-methylcyclopropyl)methyl, 1-methylcyclobutyl, (2- fluorocyclopropyl)methyl, (2,2-difluoro-3-methylcyclopropyl)methyl, (2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, 3-(trifluoromethyl)cyclobutyl, and 2- fluoropropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, cyclobutyl, butyl, propyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, ethyl, ethyl-d5, isopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, 3-fluoropropyl, 2,2-difluoroethyl, 4,4,4-trifluorobutyl, (3,3- difluorocyclobutyl)methyl, (2,2-difluorocyclopropyl)methyl, (2-methylcyclopropyl)methyl, 3- fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (1-methylcyclopropyl)methyl, (2- fluorocyclopropyl)methyl, (2,2-difluoro-3-methylcyclopropyl)methyl, (2,2- dimethylcyclopropyl)methyl, 3-(trifluoromethyl)cyclobutyl, 2-fluoropropyl, (cuban-1-yl)methyl, and (bicyclo[1.1.1]pentan-1-yl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, cyclobutyl, butyl, propyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, ethyl, isopropyl, (cyclopropyl)methyl, 3-fluoropropyl, 2,2- difluoroethyl, 4,4,4-trifluorobutyl, (3,3-difluorocyclobutyl)methyl, (2,2-difluorocyclopropyl)methyl, (2-methylcyclopropyl)methyl, 3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (1- methylcyclopropyl)methyl, (2-fluorocyclopropyl)methyl, (2,2-difluoro-3-methylcyclopropyl)methyl, (2,2-dimethylcyclopropyl)methyl, 3-(trifluoromethyl)cyclobutyl, and 2-fluoropropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2- (cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2-fluoro-2- methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1- fluorocyclopropyl)methyl, ethyl, ethyl-d ₅ , isopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , 3- fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 2,2-difluoroethyl, ((R)-oxetan-2- yl)methyl, (S)-3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3- fluorobicyclo[1.1.1]pentan-1-yl)methyl, ((S)-2,2-difluorocyclopropyl)methyl, ((R)-2,2- difluorocyclopropyl)methyl, 2-(trifluoromethoxy)ethyl, (1-methylcyclobutyl)methyl, (2- methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, (1r,3R)-3-fluorocyclobutyl, (1s,3S)-3- fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (1-methylcyclopropyl)methyl, 1- methylcyclobutyl, ((1R,2S)-2-fluorocyclopropyl)methyl, ((1S,2R)-2-fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3-methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro-3- methylcyclopropyl)methyl, ((1S,2S)-2-fluorocyclopropyl)methyl, ((S)-2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1s,3S)-3-(trifluoromethyl)cyclobutyl, (R)-2-fluoropropyl, (S)-2-fluoropropyl, (cuban-1-yl)methyl, (bicyclo[1.1.1]pentan-1-yl)methyl, and (bicyclo[2.1.1]hexan-1-yl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, (1-fluorocyclobutyl)methyl, cyclobutyl, 2- (cyano(cyclopropyl)methoxy)ethyl, butyl, propyl, (1-hydroxycyclobutyl)methyl, 2-fluoro-2- methylpropyl, methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1- fluorocyclopropyl)methyl, ethyl, isopropyl, (cyclopropyl)methyl, 3-fluoropropyl, 2-fluoroethyl, 2-((2- cyanopropan-2-yl)oxy)ethyl, 2,2-difluoroethyl, ((R)-oxetan-2-yl)methyl, (S)-3,3,3-trifluoro-2- hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl, ((S)-2,2-difluorocyclopropyl)methyl, ((R)-2,2-difluorocyclopropyl)methyl, 2-(trifluoromethoxy)ethyl, (1-methylcyclobutyl)methyl, (2-methylcyclopropyl)methyl, (2,2-difluorocyclopentyl)methyl, (1r,3R)- 3-fluorocyclobutyl, (1s,3S)-3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (1- methylcyclopropyl)methyl, 1-methylcyclobutyl, ((1R,2S)-2-fluorocyclopropyl)methyl, ((1S,2R)-2- fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3-methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro- 3-methylcyclopropyl)methyl, ((1S,2S)-2-fluorocyclopropyl)methyl, ((S)-2,2- dimethylcyclopropyl)methyl, (3,3-difluorocyclopentyl)methyl, (1s,3S)-3-(trifluoromethyl)cyclobutyl, (R)-2-fluoropropyl, and (S)-2-fluoropropyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, cyclobutyl, butyl, propyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, ethyl, ethyl-d5, isopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, 3-fluoropropyl, 2,2-difluoroethyl, 4,4,4-trifluorobutyl, (3,3- difluorocyclobutyl)methyl, ((S)-2,2-difluorocyclopropyl)methyl, ((R)-2,2-difluorocyclopropyl)methyl, (2-methylcyclopropyl)methyl, (1s,3S)-3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan- 2-yl, (1-methylcyclopropyl)methyl, ((1R,2S)-2-fluorocyclopropyl)methyl, ((1S,2R)-2- fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3-methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro- 3-methylcyclopropyl)methyl, ((1S,2S)-2-fluorocyclopropyl)methyl, ((S)-2,2- dimethylcyclopropyl)methyl, (1s,3S)-3-(trifluoromethyl)cyclobutyl, and (R)-2-fluoropropyl, (cuban-1- yl)methyl, and (bicyclo[1.1.1]pentan-1-yl)methyl. In some embodiments, R ¹ is selected from: (cyclopentyl)methyl, isobutyl, cyclopentyl, (cyclobutyl)methyl, isopentyl, cyclobutyl, butyl, propyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, ethyl, isopropyl, (cyclopropyl)methyl, 3-fluoropropyl, 2,2- difluoroethyl, 4,4,4-trifluorobutyl, (3,3-difluorocyclobutyl)methyl, ((S)-2,2- difluorocyclopropyl)methyl, ((R)-2,2-difluorocyclopropyl)methyl, (2-methylcyclopropyl)methyl, (1s,3S)-3-fluorocyclobutyl, 3,3-dimethylcyclobutyl, spiro[3.3]heptan-2-yl, (1- methylcyclopropyl)methyl, ((1R,2S)-2-fluorocyclopropyl)methyl, ((1S,2R)-2- fluorocyclopropyl)methyl, ((1S,3R)-2,2-difluoro-3-methylcyclopropyl)methyl, ((1R,3S)-2,2-difluoro- 3-methylcyclopropyl)methyl, ((1S,2S)-2-fluorocyclopropyl)methyl, ((S)-2,2- dimethylcyclopropyl)methyl, (1s,3S)-3-(trifluoromethyl)cyclobutyl, and (R)-2-fluoropropyl. One embodiment pertains to a compound of Formula (Ie): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ is selected from: C3-C7-cycloalkyl-C1-C4-alkylene, C1-C6-alkyl, C3-C7-cycloalkyl, C1-C4- alkyl-O-C2-C4-alkylene, 3-7-membered-heterocyclyl, 3-7-membered-heterocyclyl-C1-C4-alkylene, and C4-C8-bicycloalkyl-C1-C4-alkylene; wherein each R ¹ group is optionally substituted with one or more substituents selected from: halogen, C1-C4-haloalkyl, cyano, and hydroxyl. In some embodiments, R ¹ is selected from: (C3-C4-cycloalkyl)CH2-, C3-C4-cycloalkyl-CD2-, C1-C5-alkyl, C3-C4-cycloalkyl, C1-C3-alkyl-O-C2-C3-alkylene, 4-membered-heterocyclyl, (4- membered-heterocyclyl)CH2-, (C5-bicycloalkyl)CH2-; wherein each R ¹ group is optionally substituted with one or more substituents selected from: halogen, C1-haloalkyl, cyano, and hydroxyl. In some embodiments, R ¹ is selected from: (C3-C4-cycloalkyl)CH2-, C1-C5-alkyl, C3-C4- cycloalkyl, C1-C3-alkyl-O-C2-C3-alkylene, 4-membered-heterocyclyl, (4-membered- heterocyclyl)CH2-, (C5-bicycloalkyl)CH2-; wherein each R ¹ group is optionally substituted with one or more substituents selected from: halogen, C1-haloalkyl, cyano, and hydroxyl. In some embodiments, R ¹ is selected from: (C3-C4-cycloalkyl)CH2-, C3-C4-cycloalkyl-CD2-, C1-C5-alkyl, C3-C4-cycloalkyl, C1-C3-alkyl-O-C2-C3-alkylene, 4-membered-heterocyclyl, and (4- membered-heterocyclyl)CH2-; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: halogen, C1-haloalkyl, cyano, and hydroxyl. In some embodiments, R ¹ is selected from: (C ₃ -C ₄ -cycloalkyl)CH ₂ -, C ₁ -C ₅ -alkyl, C ₃ -C ₄ - cycloalkyl, C ₁ -C ₃ -alkyl-O-C ₂ -C ₃ -alkylene, 4-membered-heterocyclyl, (4-membered- heterocyclyl)CH ₂ -, (C ₅ -bicycloalkyl)CH ₂ -; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: halogen, C ₁ -haloalkyl, cyano, and hydroxyl. In some embodiments, R ¹ is selected from: methyl, methyl-d ₃ , propyl, ethyl, ethyl-d ₅ , cyclopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , isopropyl, methoxyethyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, butyl, methoxypropyl, (cyclobutyl)methyl, and pentyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, hydroxyl, cyano, and difluoromethyl. In some embodiments, R ¹ is selected from: methyl, propyl, ethyl, cyclopropyl, (cyclopropyl)methyl, isopropyl, methoxyethyl, ((propyl)oxy)ethyl, oxetanyl, (oxetanyl)methyl, butyl, methoxypropyl, (cyclobutyl)methyl, pentyl, and (bicyclo[1.1.1]pentanyl)methyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, hydroxyl, cyano, and difluoromethyl. In some embodiments, R ¹ is selected from: methyl, methyl-d3, propyl, ethyl, ethyl-d5, cyclopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, isopropyl, 2-methoxyethyl, 2-((propan-2- yl)oxy)ethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, butyl, 3-methoxypropyl, (cyclobutyl)methyl, and pentyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, hydroxyl, cyano, and difluoromethyl. In some embodiments, R ¹ is selected from: methyl, propyl, ethyl, cyclopropyl, (cyclopropyl)methyl, isopropyl, 2-methoxyethyl, 2-((propan-2-yl)oxy)ethyl, oxetan-3-yl, (oxetan-3- yl)methyl, (oxetan-2-yl)methyl, butyl, 3-methoxypropyl, (cyclobutyl)methyl, pentyl, and (bicyclo[1.1.1]pentan-1-yl)methyl; wherein each R ¹ group is optionally substituted with one, two, three, or four substituents selected from: fluoro, hydroxyl, cyano, and difluoromethyl. In some embodiments, R ¹ is selected from: methyl, methyl-d3, 2,2-difluoropropyl, 2,2,2- trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, 2-hydroxypropyl, ethyl, ethyl-d ₅ , isopropyl, 2-methoxyethyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , 3- fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, and (2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is selected from: methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, 2-hydroxypropyl, ethyl, isopropyl, 2- methoxyethyl, (cyclopropyl)methyl, 3-fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, oxetan-3-yl, (oxetan-3-yl)methyl, (oxetan-2-yl)methyl, 3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3- fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, and (2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is selected from: methyl, methyl-d ₃ , 2,2-difluoropropyl, 2,2,2- trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, (R)-2-hydroxypropyl, ethyl, ethyl-d5, isopropyl, 2-methoxyethyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, 3- fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2-yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2- difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, ((R)-oxetan-2-yl)methyl, (S)-3,3,3-trifluoro-2- hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3-difluorocyclobutyl)methyl, (1- (difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3-fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, ((S)-2,2-difluorocyclopropyl)methyl, and ((R)-2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is selected from: methyl, 2,2-difluoropropyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, (1-fluorocyclopropyl)methyl, (R)-2-hydroxypropyl, ethyl, isopropyl, 2-methoxyethyl, (cyclopropyl)methyl, 3-fluoropropyl, 2-fluoroethyl, 2-((2-cyanopropan-2- yl)oxy)ethyl, 1,1,1-trifluoropropan-2-yl, 2,2-difluoroethyl, oxetan-3-yl, oxetan-3-ylmethyl, ((R)- oxetan-2-yl)methyl, (S)-3,3,3-trifluoro-2-hydroxypropyl, 4,4,4-trifluorobutyl, 3-methoxypropyl, (3,3- difluorocyclobutyl)methyl, (1-(difluoromethyl)cyclopropyl)methyl, 5,5,5-trifluoropentyl, (3- fluorobicyclo[1.1.1]pentan-1-yl)methyl, fluoromethyl, ((S)-2,2-difluorocyclopropyl)methyl, and ((R)- 2,2-difluorocyclopropyl)methyl. One embodiment pertains to a compound of Formula (Ie): , or a pharmaceutically acceptable salt thereof, wherein: R ¹ is selected from: C1-C6-alkyl, C3-C7-cycloalkyl, and C3-C7-cycloalkyl-C1-C4-alkylene; wherein each group is optionally substituted with one or more halogen substituents. In some embodiments, R ¹ is selected from: C1-C6-alkyl, C3-C7-cycloalkyl, and C3-C7- cycloalkyl-C1-C4-alkylene; wherein each group is optionally substituted with one, two, or three halogen substituents. In some embodiments, R ¹ is selected from: C ₂ -C ₃ -alkyl, cyclopropyl, C ₃ -C ₄ -cycloalkyl-CD ₂ -, and C ₃ -C ₄ -cycloalkyl-CH ₂ -; wherein each group is optionally substituted with one, two, or three halogen substituents. In some embodiments, R ¹ is selected from: C ₂ -C ₃ -alkyl, cyclopropyl, and C ₃ -C ₄ -cycloalkyl- CH ₂ -; wherein each group is optionally substituted with one, two, or three halogen substituents. In some embodiments, R ¹ is selected from: ethyl, propyl, cyclopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , and (cyclobutyl)methyl; wherein each group is optionally substituted with one, two, or three halogen substituents. In some embodiments, R ¹ is selected from: ethyl, propyl, cyclopropyl, (cyclopropyl)methyl, and (cyclobutyl)methyl; wherein each group is optionally substituted with one, two, or three halogen substituents. In some embodiments, R ¹ is selected from: ethyl, propyl, cyclopropyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, and (cyclobutyl)methyl; wherein each group is optionally substituted with one, two, or three fluoro substituents. In some embodiments, R ¹ is selected from: ethyl, propyl, cyclopropyl, (cyclopropyl)methyl, and (cyclobutyl)methyl; wherein each group is optionally substituted with one, two, or three fluoro substituents. In some embodiments, R ¹ is selected from: 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, ethyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, (3,3-difluorocyclobutyl)methyl, and (2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is selected from: 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, ethyl, (cyclopropyl)methyl, (3,3-difluorocyclobutyl)methyl, and (2,2- difluorocyclopropyl)methyl. In some embodiments, R ¹ is selected from: 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, ethyl, (cyclopropyl)methyl, (cyclopropyl)methyl-d2, (3,3-difluorocyclobutyl)methyl, ((S)-2,2-difluorocyclopropyl)methyl, and ((R)-2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is selected from: 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, cyclopropyl, ethyl, (cyclopropyl)methyl, (3,3-difluorocyclobutyl)methyl, ((S)-2,2- difluorocyclopropyl)methyl, and ((R)-2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is C3-C7-cycloalkyl-C1-C4-alkylene optionally substituted with one or two halogen substituents. In some embodiments, R ¹ is selected from: (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , and (cyclobutyl)methyl; wherein each group is optionally substituted with one or two halogen substituents. In some embodiments, R ¹ is (cyclopropyl)methyl or (cyclobutyl)methyl; wherein each group is optionally substituted with one or two halogen substituents. In some embodiments, R ¹ is selected from: (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , and (cyclobutyl)methyl; wherein each group is optionally substituted with one or two fluoro substituents. In some embodiments, R ¹ is (cyclopropyl)methyl or (cyclobutyl)methyl; wherein each group is optionally substituted with one or two fluoro substituents. In some embodiments, R ¹ is selected from: (cyclopropyl)methyl, (cyclopropyl)methyl-d ₂ , (3,3-difluorocyclobutyl)methyl, and (2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is selected from: (cyclopropyl)methyl, (3,3- difluorocyclobutyl)methyl, and (2,2-difluorocyclopropyl)methyl. In some embodiments, R ¹ is selected from: (cyclopropyl)methyl, (cyclopropyl)methyl-d2, and (cyclobutyl)methyl; wherein each group is optionally substituted with one or two halogen substituents. In some embodiments, R ¹ is C1-C6-alkyl optionally substituted with one, two, or three halogen substituents. In some embodiments, R ¹ is ethyl or propyl; wherein each group is optionally substituted with one, two, or three halogen substituents. In some embodiments, R ¹ is ethyl or propyl; wherein each group is optionally substituted with one, two, or three fluoro substituents. In some embodiments, R ¹ is selected from: 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, and ethyl. In some embodiments, R ¹ is C3-C7-cycloalkyl. In some embodiments, R ¹ is cyclopropyl. Some embodiments include every combination of one or more compounds and pharmaceutically acceptable salts thereof selected from the following group of compounds shown in Table A. Some embodiments include every combination of one or more compounds selected from the following group shown in Table A. Table A 1 Mixture of trans isomers (cyclopropyl). 2 Mixture of cis isomers (cyclopropyl). Some embodiments of the present invention include every combination of one or more compounds selected from the following group: (2R,3R,11bR)-3-(tert-butoxy)-9- (cyclopentylmethoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-p yrido[2,1-a]isoquinolin-2-ol (Compound 1); (2R,3R,11bR)-3-(tert-butoxy)-9-isobutoxy-10-methoxy-1,3,4,6, 7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 2); (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopentyloxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 3); (2R,3R,11bR)-3- (tert-butoxy)-9-(cyclobutylmethoxy)-10-methoxy-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 4); 2-(1-((((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-9-yl)oxy )methyl)cyclopropyl)acetonitrile (Compound 5); (2R,3R,11bR)-3-(tert-butoxy)-9-(isopentyloxy)-10-methoxy-1,3 ,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 6); (2R,3R,11bR)-3-(tert-butoxy)-9-((1- fluorocyclobutyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro -2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 7); (2R,3R,11bR)-3-(tert-butoxy)-9-cyclobutoxy-10-methoxy-1,3,4, 6,7,11b-hexahydro- 2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 8); 2-(2-(((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 9-yl)oxy)ethoxy)-2- cyclopropylacetonitrile (Compound 9); (2R,3R,11bR)-3-(tert-butoxy)-9-butoxy-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 10); (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-propoxy-1,3,4,6,7,11b-hexahydro-2H-pyri do[2,1-a]isoquinolin-2-ol (Compound 11); (2R,3R,11bR)-3-(tert-butoxy)-9-((1-hydroxycyclobutyl)methoxy )-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 12); (2R,3R,11bR)-3-(tert- butoxy)-9-(2-cyclopropoxyethoxy)-10-methoxy-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 13); (2R,3R,11bR)-3-(tert-butoxy)-9-(2-fluoro-2-methylpropoxy)-10 - methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 14); (2R,3R,11bR)- 3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py rido[2,1-a]isoquinolin-2-ol (Compound 15); (2R,3R,11bR)-3-(tert-butoxy)-9-(2,2-difluoropropoxy)-10-meth oxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 16); (2R,3R,11bR)-3-(tert-butoxy)-10- methoxy-9-(2,2,2-trifluoroethoxy)-1,3,4,6,7,11b-hexahydro-2H -pyrido[2,1-a]isoquinolin-2-ol (Compound 17); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(3,3,3-trifluoropr opoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 18); (2R,3R,11bR)-3-(tert-butoxy)-9- cyclopropoxy-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2, 1-a]isoquinolin-2-ol (Compound 19); (2R,3R,11bR)-3-(tert-butoxy)-9-((1-fluorocyclopropyl)methoxy )-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 20); (2R,3R,11bR)-3-(tert-butoxy)-9-((R)- 2-hydroxypropoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyri do[2,1-a]isoquinolin-2-ol (Compound 21); (2R,3R,11bR)-3-(tert-butoxy)-9-ethoxy-10-methoxy-1,3,4,6,7,1 1b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 22); (2R,3R,11bR)-3-(tert-butoxy)-9-isopropoxy-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 23); (2R,3R,11bR)- 3-(tert-butoxy)-10-methoxy-9-(2-methoxyethoxy)-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 24); (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopropylmethoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 25); (2R,3R,11bR)- 3-(tert-butoxy)-9-(3-fluoropropoxy)-10-methoxy-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 26); (2R,3R,11bR)-3-(tert-butoxy)-9-(2-fluoroethoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 27); (2R,3R,11bR)-3-(tert- butoxy)-9-(2-fluoroethoxy)-10-methoxy-1,3,4,6,7,11b-hexahydr o-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 28); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1,1,1-trifluorop ropan-2-yl)oxy)- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 29); (2R,3R,11bR)-3-(tert- butoxy)-9-(ethoxy-d5)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 30); (2R,3R,11bR)-3-(tert-butoxy)-9-(2,2-difluoroethoxy)-10-metho xy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 31); (2R,3R,11bR)-3-(tert-butoxy)-10- methoxy-9-(oxetan-3-yloxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1-a]isoquinolin-2-ol (Compound 32); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(oxetan-3-ylmethox y)-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 33); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(((R)- oxetan-2-yl)methoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a ]isoquinolin-2-ol (Compound 34); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((S)-3,3,3-trifluo ro-2-hydroxypropoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 35); (2R,3R,11bR)-3-(tert-butoxy)-10- methoxy-9-(4,4,4-trifluorobutoxy)-1,3,4,6,7,11b-hexahydro-2H -pyrido[2,1-a]isoquinolin-2-ol (Compound 36); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(3-methoxypropoxy) -1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 37); (2R,3R,11bR)-3-(tert-butoxy)-9-((3,3- difluorocyclobutyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 38); (2R,3R,11bR)-3-(tert-butoxy)-9-((1-(difluoromethyl)cycloprop yl)methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 39); (2R,3R,11bR)- 3-(tert-butoxy)-10-methoxy-9-((5,5,5-trifluoropentyl)oxy)-1, 3,4,6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 40); (2R,3R,11bR)-3-(tert-butoxy)-9-((3-fluorobicyclo[1.1.1]penta n- 1-yl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2 ,1-a]isoquinolin-2-ol (Compound 41); (2R,3R,11bR)-3-(tert-butoxy)-9-(fluoromethoxy)-10-methoxy-1, 3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 42); (2R,3R,11bR)-3-(tert-butoxy)-9-(((S)-2,2- difluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1-a]isoquinolin-2- ol (Compound 43); (2R,3R,11bR)-3-(tert-butoxy)-9-(((R)-2,2-difluorocyclopropyl )methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 44); (2R,3R,11bR)- 3-(tert-butoxy)-10-methoxy-9-(2-(trifluoromethoxy)ethoxy)-1, 3,4,6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 45); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(neopentyloxy)- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 46); (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-((1-methylcyclobutyl)methoxy)-1,3,4,6,7 ,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 47); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((2- methylcyclopropyl)methoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1-a]isoquinolin-2-ol (Compound 48); (2R,3R,11bR)-3-(tert-butoxy)-9-((2,2-difluorocyclopentyl)met hoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 49); (2R,3R,11bR)-3-(tert-butoxy)-9-((3- fluorocyclobut-2-en-1-yl)oxy)-10-methoxy-1,3,4,6,7,11b-hexah ydro-2H-pyrido[2,1-a]isoquinolin-2- ol (Compound 50); (2R,3R,11bR)-9-((2-oxaspiro[3.3]heptan-6-yl)oxy)-3-(tert-but oxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 51); (1R,3r)-3- (((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methoxy-1,3,4,6, 7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-9-yl)oxy)cyclobutane-1-carbonitrile (Compound 52); (2R,3R,11bR)-3-(tert-butoxy)-9- ((1r,3R)-3-fluorocyclobutoxy)-10-methoxy-1,3,4,6,7,11b-hexah ydro-2H-pyrido[2,1-a]isoquinolin-2- ol (Compound 53); (2R,3R,11bR)-3-(tert-butoxy)-9-((1s,3S)-3-fluorocyclobutoxy) -10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 54); (2R,3R,11bR)-3-(tert- butoxy)-9-(3,3-dimethylcyclobutoxy)-10-methoxy-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 55); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(spiro[3.3]heptan- 2- yloxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2 -ol (Compound 56); (2R,3R,11bR)-3- (tert-butoxy)-10-methoxy-9-((1-methylpyrrolidin-3-yl)oxy)-1, 3,4,6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 57); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((3-methyloxetan-3 - yl)methoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquino lin-2-ol (Compound 58); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1-methylcyclopro pyl)methoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 59); (2R,3R,11bR)-3-(tert-butoxy)-10- methoxy-9-(1-methylcyclobutoxy)-1,3,4,6,7,11b-hexahydro-2H-p yrido[2,1-a]isoquinolin-2-ol (Compound 60); (2R,3R,11bR)-3-(tert-butoxy)-9-(((1R,2S)-2-fluorocyclopropyl )methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 61); (2R,3R,11bR)- 3-(tert-butoxy)-9-(((1S,2R)-2-fluorocyclopropyl)methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 62); (2R,3R,11bR)-3-(tert-butoxy)-9-(((1S,3R)-2,2- difluoro-3-methylcyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,1 1b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 63); (2R,3R,11bR)-3-(tert-butoxy)-9-(((1R,3S)-2,2-difluoro-3- methylcyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydr o-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 64); (2R,3R,11bR)-3-(tert-butoxy)-9-((S)-1-cyclobutylethoxy)-10-m ethoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 65); (2R,3R,11bR)-3-(tert- butoxy)-9-((R)-1-cyclobutylethoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 66); (2R,3R,11bR)-3-(tert-butoxy)-9-(((1S,2S)-2- fluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydr o-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 67); (2R,3R,11bR)-3-(tert-butoxy)-9-(((1R,2R)-2-fluorocyclopropyl )methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 68); (2R,3R,11bR)- 3-(tert-butoxy)-9-(((S)-2,2-dimethylcyclopropyl)methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 69); (2R,3R,11bR)-3-(tert-butoxy)-9-((3,3- difluorocyclopentyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 70); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1s,3S)-3- (trifluoromethyl)cyclobutoxy)-1,3,4,6,7,11b-hexahydro-2H-pyr ido[2,1-a]isoquinolin-2-ol (Compound 71); (2R,3R,11bR)-3-(tert-butoxy)-9-((R)-2-fluoropropoxy)-10-meth oxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 72); (2R,3R,11bR)-3-(tert-butoxy)-9-((S)-2- fluoropropoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[ 2,1-a]isoquinolin-2-ol (Compound 73); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1s,3S)-3-methoxy cyclobutoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 74); (2R,3R,11bR)-3-(tert-butoxy)-9- ((1s,3S)-3-(dimethylamino)cyclobutoxy)-10-methoxy-1,3,4,6,7, 11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 75); (2S,3R,11bR)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 76); (2S,3S,11bS)-3-(tert-butoxy)-9,10- dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoli n-2-ol (Compound 77); (2R,3S,11bS)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 78); 2-(((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methoxy-1,3,4, 6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-9-yl)oxy)acetonitrile (Compound 79); (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-(methoxy-d3)-1,3,4,6,7,11b-hexahydro-2H -pyrido[2,1-a]isoquinolin-2-ol (Compound 80); 1-((((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methoxy-1,3,4 ,6,7,11b-hexahydro- 2H-pyrido[2,1-a]isoquinolin-9-yl)oxy)methyl)cyclobutane-1-ca rbonitrile (Compound 81); 1- ((((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methoxy-1,3,4,6 ,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-9-yl)oxy)methyl)cyclopropane-1-carbonitrile (Compound 82); (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-((R)-3,3,3-trifluoro-2-hydroxypropoxy)- 1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 83); (2R,3R,11bR)-3-(tert-butoxy)-9-((S)-2- hydroxypropoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1-a]isoquinolin-2-ol (Compound 84); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((R)-2-methoxyprop oxy)- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 85); (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-((S)-2-methoxypropoxy)-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 86); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1- (methylsulfonyl)cyclopropyl)methoxy)-1,3,4,6,7,11b-hexahydro -2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 87); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(3-(methylsulfonyl )propoxy)- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 88); (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-(2-(methylsulfonyl)ethoxy)-1,3,4,6,7,11 b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 89); (2R,3R,11bR)-3-(tert-butoxy)-9-(3,3-difluorocyclobutoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 90); (2R,3R,11bR)- 3-(tert-butoxy)-9-((2,2-difluorocyclobutyl)methoxy)-10-metho xy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 91); (1S,3s)-3-(((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy- 10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinol in-9-yl)oxy)cyclobutane-1- carbonitrile (Compound 92); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1r,3R)-3- (trifluoromethyl)cyclobutoxy)-1,3,4,6,7,11b-hexahydro-2H-pyr ido[2,1-a]isoquinolin-2-ol (Compound 93); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1r,3R)-3-methoxy cyclobutoxy)- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 94); and (2R,3R,11bR)-3- (tert-butoxy)-9-((1r,3R)-3-(dimethylamino)cyclobutoxy)-10-me thoxy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 95); trans-(2R,3R,11bR)-3-(tert-butoxy)-9-((2- fluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydr o-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 96); trans-(2R,3R,11bR)-3-(tert-butoxy)-9-((2,2-difluoro-3- methylcyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydr o-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 97); and cis-(2R,3R,11bR)-3-(tert-butoxy)-9-((2-fluorocyclopropyl)met hoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 98); or a pharmaceutically acceptable salt thereof. Some embodiments of the present invention include every combination of one or more compounds selected from the following group: (2R,3R,11bR)-3-(tert-butoxy)-9- (cyclopentylmethoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-p yrido[2,1-a]isoquinolin-2-ol (Compound 1); (2R,3R,11bR)-3-(tert-butoxy)-9-isobutoxy-10-methoxy-1,3,4,6, 7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 2); (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopentyloxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 3); (2R,3R,11bR)-3- (tert-butoxy)-9-(cyclobutylmethoxy)-10-methoxy-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 4); 2-(1-((((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-9-yl)oxy )methyl)cyclopropyl)acetonitrile (Compound 5); (2R,3R,11bR)-3-(tert-butoxy)-9-(isopentyloxy)-10-methoxy-1,3 ,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 6); (2R,3R,11bR)-3-(tert-butoxy)-9-((1- fluorocyclobutyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro -2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 7); (2R,3R,11bR)-3-(tert-butoxy)-9-cyclobutoxy-10-methoxy-1,3,4, 6,7,11b-hexahydro- 2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 8); 2-(2-(((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 9-yl)oxy)ethoxy)-2- cyclopropylacetonitrile (Compound 9); (2R,3R,11bR)-3-(tert-butoxy)-9-butoxy-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 10); (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-propoxy-1,3,4,6,7,11b-hexahydro-2H-pyri do[2,1-a]isoquinolin-2-ol (Compound 11); (2R,3R,11bR)-3-(tert-butoxy)-9-((1-hydroxycyclobutyl)methoxy )-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 12); (2R,3R,11bR)-3-(tert- butoxy)-9-(2-cyclopropoxyethoxy)-10-methoxy-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 13); (2R,3R,11bR)-3-(tert-butoxy)-9-(2-fluoro-2-methylpropoxy)-10 - methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 14); (2R,3R,11bR)- 3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-py rido[2,1-a]isoquinolin-2-ol (Compound 15); (2R,3R,11bR)-3-(tert-butoxy)-9-(2,2-difluoropropoxy)-10-meth oxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 16); (2R,3R,11bR)-3-(tert-butoxy)-10- methoxy-9-(2,2,2-trifluoroethoxy)-1,3,4,6,7,11b-hexahydro-2H -pyrido[2,1-a]isoquinolin-2-ol (Compound 17); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(3,3,3-trifluoropr opoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 18); (2R,3R,11bR)-3-(tert-butoxy)-9- cyclopropoxy-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2, 1-a]isoquinolin-2-ol (Compound 19); (2R,3R,11bR)-3-(tert-butoxy)-9-((1-fluorocyclopropyl)methoxy )-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 20); (2R,3R,11bR)-3-(tert-butoxy)-9-((R)- 2-hydroxypropoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyri do[2,1-a]isoquinolin-2-ol (Compound 21); (2R,3R,11bR)-3-(tert-butoxy)-9-ethoxy-10-methoxy-1,3,4,6,7,1 1b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 22); (2R,3R,11bR)-3-(tert-butoxy)-9-isopropoxy-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 23); (2R,3R,11bR)- 3-(tert-butoxy)-10-methoxy-9-(2-methoxyethoxy)-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 24); (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopropylmethoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 25); (2R,3R,11bR)- 3-(tert-butoxy)-9-(3-fluoropropoxy)-10-methoxy-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 26); (2R,3R,11bR)-3-(tert-butoxy)-9-(2-fluoroethoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 27); (2R,3R,11bR)-3-(tert- butoxy)-9-(2-fluoroethoxy)-10-methoxy-1,3,4,6,7,11b-hexahydr o-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 28); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1,1,1-trifluorop ropan-2-yl)oxy)- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 29); (2R,3R,11bR)-3-(tert- butoxy)-9-(ethoxy-d5)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 30); (2R,3R,11bR)-3-(tert-butoxy)-9-(2,2-difluoroethoxy)-10-metho xy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 31); (2R,3R,11bR)-3-(tert-butoxy)-10- methoxy-9-(oxetan-3-yloxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1-a]isoquinolin-2-ol (Compound 32); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(oxetan-3-ylmethox y)-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 33); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(((R)- oxetan-2-yl)methoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a ]isoquinolin-2-ol (Compound 34); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((S)-3,3,3-trifluo ro-2-hydroxypropoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 35); (2R,3R,11bR)-3-(tert-butoxy)-10- methoxy-9-(4,4,4-trifluorobutoxy)-1,3,4,6,7,11b-hexahydro-2H -pyrido[2,1-a]isoquinolin-2-ol (Compound 36); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(3-methoxypropoxy) -1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 37); (2R,3R,11bR)-3-(tert-butoxy)-9-((3,3- difluorocyclobutyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 38); (2R,3R,11bR)-3-(tert-butoxy)-9-((1-(difluoromethyl)cycloprop yl)methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 39); (2R,3R,11bR)- 3-(tert-butoxy)-10-methoxy-9-((5,5,5-trifluoropentyl)oxy)-1, 3,4,6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 40); (2R,3R,11bR)-3-(tert-butoxy)-9-((3-fluorobicyclo[1.1.1]penta n- 1-yl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2 ,1-a]isoquinolin-2-ol (Compound 41); (2R,3R,11bR)-3-(tert-butoxy)-9-(fluoromethoxy)-10-methoxy-1, 3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 42); (2R,3R,11bR)-3-(tert-butoxy)-9-(((S)-2,2- difluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1-a]isoquinolin-2- ol (Compound 43); (2R,3R,11bR)-3-(tert-butoxy)-9-(((R)-2,2-difluorocyclopropyl )methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 44); (2R,3R,11bR)- 3-(tert-butoxy)-10-methoxy-9-(2-(trifluoromethoxy)ethoxy)-1, 3,4,6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 45); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(neopentyloxy)- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 46); (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-((1-methylcyclobutyl)methoxy)-1,3,4,6,7 ,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 47); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((2- methylcyclopropyl)methoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1-a]isoquinolin-2-ol (Compound 48); (2R,3R,11bR)-3-(tert-butoxy)-9-((2,2-difluorocyclopentyl)met hoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 49); (2R,3R,11bR)-3-(tert-butoxy)-9-((3- fluorocyclobut-2-en-1-yl)oxy)-10-methoxy-1,3,4,6,7,11b-hexah ydro-2H-pyrido[2,1-a]isoquinolin-2- ol (Compound 50); (2R,3R,11bR)-9-((2-oxaspiro[3.3]heptan-6-yl)oxy)-3-(tert-but oxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 51); (1R,3r)-3- (((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methoxy-1,3,4,6, 7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-9-yl)oxy)cyclobutane-1-carbonitrile (Compound 52); (2R,3R,11bR)-3-(tert-butoxy)-9- ((1r,3R)-3-fluorocyclobutoxy)-10-methoxy-1,3,4,6,7,11b-hexah ydro-2H-pyrido[2,1-a]isoquinolin-2- ol (Compound 53); (2R,3R,11bR)-3-(tert-butoxy)-9-((1s,3S)-3-fluorocyclobutoxy) -10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 54); (2R,3R,11bR)-3-(tert- butoxy)-9-(3,3-dimethylcyclobutoxy)-10-methoxy-1,3,4,6,7,11b -hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 55); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(spiro[3.3]heptan- 2- yloxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2 -ol (Compound 56); (2R,3R,11bR)-3- (tert-butoxy)-10-methoxy-9-((3-methyloxetan-3-yl)methoxy)-1, 3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 58); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1- methylcyclopropyl)methoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1-a]isoquinolin-2-ol (Compound 59); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(1-methylcyclobuto xy)-1,3,4,6,7,11b-hexahydro- 2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 60); (2R,3R,11bR)-3-(tert-butoxy)-9-(((1R,2S)-2- fluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydr o-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 61); (2R,3R,11bR)-3-(tert-butoxy)-9-(((1S,2R)-2-fluorocyclopropyl )methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 62); (2R,3R,11bR)- 3-(tert-butoxy)-9-(((1S,3R)-2,2-difluoro-3-methylcyclopropyl )methoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 63); (2R,3R,11bR)-3-(tert-butoxy)-9- (((1R,3S)-2,2-difluoro-3-methylcyclopropyl)methoxy)-10-metho xy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 64); (2R,3R,11bR)-3-(tert-butoxy)-9-((S)-1- cyclobutylethoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyri do[2,1-a]isoquinolin-2-ol (Compound 65); (2R,3R,11bR)-3-(tert-butoxy)-9-((R)-1-cyclobutylethoxy)-10-m ethoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 66); (2R,3R,11bR)-3-(tert- butoxy)-9-(((1S,2S)-2-fluorocyclopropyl)methoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 67); (2R,3R,11bR)-3-(tert-butoxy)-9-(((1R,2R)-2- fluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahydr o-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 68); (2R,3R,11bR)-3-(tert-butoxy)-9-(((S)-2,2-dimethylcyclopropyl )methoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 69); (2R,3R,11bR)- 3-(tert-butoxy)-9-((3,3-difluorocyclopentyl)methoxy)-10-meth oxy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 70); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1s,3S)- 3-(trifluoromethyl)cyclobutoxy)-1,3,4,6,7,11b-hexahydro-2H-p yrido[2,1-a]isoquinolin-2-ol (Compound 71); (2R,3R,11bR)-3-(tert-butoxy)-9-((R)-2-fluoropropoxy)-10-meth oxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 72); (2R,3R,11bR)-3-(tert-butoxy)-9-((S)-2- fluoropropoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[ 2,1-a]isoquinolin-2-ol (Compound 73); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1s,3S)-3-methoxy cyclobutoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 74); (2S,3R,11bR)-3-(tert-butoxy)-9,10- dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoli n-2-ol (Compound 76); 2- (((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methoxy-1,3,4,6, 7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-9-yl)oxy)acetonitrile (Compound 79); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9- (methoxy-d3)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquin olin-2-ol (Compound 80); 1- ((((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methoxy-1,3,4,6 ,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-9-yl)oxy)methyl)cyclobutane-1-carbonitrile (Compound 81); 1-((((2R,3R,11bR)-3- (tert-butoxy)-2-hydroxy-10-methoxy-1,3,4,6,7,11b-hexahydro-2 H-pyrido[2,1-a]isoquinolin-9- yl)oxy)methyl)cyclopropane-1-carbonitrile (Compound 82); (2R,3R,11bR)-3-(tert-butoxy)-10- methoxy-9-((R)-3,3,3-trifluoro-2-hydroxypropoxy)-1,3,4,6,7,1 1b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 83); (2R,3R,11bR)-3-(tert-butoxy)-9-((S)-2-hydroxypropoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 84); (2R,3R,11bR)- 3-(tert-butoxy)-10-methoxy-9-((R)-2-methoxypropoxy)-1,3,4,6, 7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 85); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((S)-2- methoxypropoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoq uinolin-2-ol (Compound 86); (2R,3R,11bR)-3-(tert-butoxy)-9-(3,3-difluorocyclobutoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 90); (2R,3R,11bR)-3-(tert-butoxy)-9-((2,2- difluorocyclobutyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 91); (1S,3s)-3-(((2R,3R,11bR)-3-(tert-butoxy)-2-hydroxy-10-methox y-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-9-yl)oxy)cyclobutane-1 -carbonitrile (Compound 92); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((1r,3R)-3-(triflu oromethyl)cyclobutoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 93); and (2R,3R,11bR)-3-(tert-butoxy)-10- methoxy-9-((1r,3R)-3-methoxycyclobutoxy)-1,3,4,6,7,11b-hexah ydro-2H-pyrido[2,1-a]isoquinolin-2- ol (Compound 94); trans-(2R,3R,11bR)-3-(tert-butoxy)-9-((2-fluorocyclopropyl)m ethoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 96); trans- (2R,3R,11bR)-3-(tert-butoxy)-9-((2,2-difluoro-3-methylcyclop ropyl)methoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 97); and cis-(2R,3R,11bR)-3- (tert-butoxy)-9-((2-fluorocyclopropyl)methoxy)-10-methoxy-1, 3,4,6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 98); or a pharmaceutically acceptable salt thereof. Some embodiments of the present invention include every combination of one or more compounds selected from the following group: (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopropylmethoxy- d2)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoqu inolin-2-ol (Compound 99); (2R,3R,11bR)-3-(tert-butoxy)-9-(cuban-1-ylmethoxy)-10-methox y-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 100); (2R,3R,11bR)-9-(bicyclo[1.1.1]pentan-1- ylmethoxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahydr o-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 101); (2R,3R,11bR)-9-(bicyclo[2.1.1]hexan-1-ylmethoxy)-3-(tert-but oxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 102); (2R,3R,11bR)-3-(tert- butoxy)-9-((1,1-dimethylsilolan-3-yl)methoxy)-10-methoxy-1,3 ,4,6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 103); (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-((3- (trifluoromethyl)bicyclo[1.1.1]pentan-1-yl)methoxy)-1,3,4,6, 7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 104); (2R,3R,11bR)-9-((2-oxabicyclo[2.1.1]hexan-1-yl)methoxy)-3- (tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2 ,1-a]isoquinolin-2-ol (Compound 105); and (2R,3R,11bR)-9-((2-oxabicyclo[2.1.1]hexan-4-yl)methoxy)-3-(t ert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 106); or a pharmaceutically acceptable salt thereof. USEFUL INTERMEDIATES Certain intermediates as described herein, supra, and infra, are novel and useful in the preparation of compounds, such as, compounds of Formula (Ia), Formula (Ic), Formula (Ie), Formula (Ig), Formula (Ii), and Formula (Ik). Certain intermediates are shown in FIG.2A and FIG.2B. In some embodiments, the compound is selected from the group consisting of: 3-(tert- butoxy)-4-(dimethylamino)butan-2-one; 1-(6-(benzyloxy)-7-methoxy-1,2,3,4-tetrahydroisoquinolin- 1-yl)-3-(tert-butoxy)propan-2-one; 9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one; 9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol; and 3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoline-2,9-dio l; or a salt thereof. In some embodiments, the compound is: 3-(tert-butoxy)-4-(dimethylamino)butan-2-one, or a salt thereof: . In some embodiments, the compound is: (R)-3-(tert-butoxy)-4-(dimethylamino)butan-2-one, or a salt thereof. In some embodiments, the compound is: (S)-3-(tert-butoxy)-4-(dimethylamino)butan-2-one, or a salt thereof. In some embodiments, the compound is selected from the group consisting of: 1-(6- (benzyloxy)-7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)-3- (tert-butoxy)propan-2-one; 9- (benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin-2- one; 9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexah ydro-2H-pyrido[2,1- a]isoquinolin-2-ol; and 3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido [2,1- a]isoquinoline-2,9-diol; or a salt thereof. In some embodiments, the compound is: 1-(6-(benzyloxy)-7-methoxy-1,2,3,4- tetrahydroisoquinolin-1-yl)-3-(tert-butoxy)propan-2-one, or a salt thereof: . In some embodiments, the compound is: (R)-1-(6-(benzyloxy)-7-methoxy-1,2,3,4- tetrahydroisoquinolin-1-yl)-3-(tert-butoxy)propan-2-one, or a salt thereof. In some embodiments, the compound is: (S)-1-(6-(benzyloxy)-7-methoxy-1,2,3,4-tetrahydroisoquinolin -1-yl)-3-(tert- butoxy)propan-2-one, or a salt thereof. In some embodiments, the compound is: 9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one, or a salt thereof. In some embodiments, the compound is: (3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7 ,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-one, or a salt thereof: . In some embodiments, the compound is: (3S,11bS)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one, or a salt thereof. In some embodiments, the compound is: 9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a salt thereof. In some embodiments, the compound is: (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4, 6,7,11b-hexahydro- 2H-pyrido[2,1-a]isoquinolin-2-ol, or a salt thereof: . In some embodiments, the salt is a (2S,3S)-2,3-bis(4-methylbenzoyloxy)butanedioic acid (DPTTA) salt. In some embodiments, the compounds is: . In some embodiments, the compound is: (2S,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol, or a salt thereof. In some embodiments, the compound is: (2R,3S,11bS)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4, 6,7,11b-hexahydro- 2H-pyrido[2,1-a]isoquinolin-2-ol, or a salt thereof. In some embodiments, the compound is: (2S,3S,11bS)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4, 6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol, or a salt thereof. In some embodiments, the compound is: 3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinoline-2,9-diol; or a salt thereof. In some embodiments, the compound is: (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1- a]isoquinoline-2,9-diol (Compound 2-22); or a salt thereof: . In some embodiments, the compound is: (2S,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinoline-2,9-diol; or a salt thereof. In some embodiments, the compound is: (2R,3S,11bS)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1- a]isoquinoline-2,9-diol; or a salt thereof. In some embodiments, the compound is: (2S,3S,11bS)-3- (tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2 ,1-a]isoquinoline-2,9-diol; or a salt thereof. It is further appreciated that certain features, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination. PHARMACEUTICAL COMPOSITIONS, FORMULATION, AND DOSAGE FORMS The present disclosure further provides for pharmaceutical products, such as, pharmaceutical compositions, formulations, unit dosage forms, and kits; each comprising a compound, as described herein, or a pharmaceutically acceptable salt thereof. The present disclosure further provides for pharmaceutical compositions comprising a compound, as described herein, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient for use in the methods described here, such as, for treating hyperkinetic movement disorders. A pharmaceutically acceptable excipient is a physiologically and pharmaceutically suitable non-toxic and inactive material or ingredient that does not interfere with the activity of the drug substance; an excipient also can be called a carrier. The formulation methods and excipients described herein are exemplary and are in no way limiting. Pharmaceutically acceptable excipients are well known in the pharmaceutical art and described, for example, in Rowe et al., Handbook of Pharmaceutical Excipients: A Comprehensive Guide to Uses, Properties, and Safety, 5 ^th Ed., 2006, and in Remington: The Science and Practice of Pharmacy (Gennaro, 21 ^st Ed. Mack Pub. Co., Easton, PA (2005)). The compositions can also be formulated as pills, capsules, granules, or tablets which contain, in addition to an VMAT2 inhibitor, diluents, dispersing and surface active agents, binders, and lubricants. One skilled in this art can further formulate the VMAT2 inhibitor in an appropriate manner, and in accordance with accepted practices, such as, those disclosed in Remington, supra. Methods of administration include systemic administration of a VMAT2 inhibitor described herein, preferably in the form of a pharmaceutical composition as discussed above. As used herein, systemic administration includes oral and parenteral methods of administration. For oral administration, suitable pharmaceutical compositions include powders, granules, pills, tablets, and capsules as well as liquids, syrups, suspensions, and emulsions. Pharmaceutical preparations for oral administration can be obtained by any suitable method, typically by uniformly mixing the compound(s) with liquids or finely divided solid carriers, or both, in the required proportions and then, if necessary, processing the mixture, after adding suitable auxiliaries, if desired, forming the resulting mixture into a desired shape to obtain tablets or dragee cores. Conventional excipients, such as, binding agents, fillers, adjuvant, carrier, acceptable wetting agents, tableting lubricants, and disintegrants can be used in tablets and capsules for oral administration. Liquid preparations for oral administration can be in the form of solutions, emulsions, aqueous or oily suspensions, and syrups. Alternatively, the oral preparations can be in the form of dry powder that can be reconstituted with water or another suitable liquid vehicle before use. Parenteral dosage forms can be prepared by dissolving the compound in a suitable liquid vehicle and filter sterilizing the solution before lyophilization, or simply filling and sealing an appropriate vial or ampule. Some embodiments provide methods for preparing a pharmaceutical composition comprising the step of admixing a compound, as described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Formulations suitable for vaginal administration can be presented as pessaries, tampons, creams, gels, pastes, foams, or sprays containing in addition to the drug substance such carriers as are known in the art to be appropriate. In making pharmaceutical compositions, the drug substance is typically mixed (i.e., admixed) with an excipient, diluted by an excipient or enclosed within such a carrier in the form of, for example, a capsule, sachet, paper, or other container. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier, or medium for the drug substance. Thus, the compositions can be in the form of tablets, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments, soft and hard gelatin capsules, suppositories, sterile injectable solutions, and sterile packaged powders. For preparing solid form pharmaceutical compositions, such as, powders, tablets, capsules, cachets, suppositories, and dispersible granules an excipient can be one or more substances which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material. Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for oral administration. Such liquid forms include solutions, suspensions, and emulsions. These preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like. For preparing suppositories, a low melting wax, such as, an admixture of fatty acid glycerides or cocoa butter, is first melted and the active component is dispersed homogeneously therein, as by stirring. The molten homogenous mixture is then poured into convenient sized molds, allowed to cool and thereby to solidify. Liquid form preparations include solutions, suspensions, and emulsions, for example, water or water-propylene glycol solutions. Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent. The pharmaceutical compositions can take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles and can contain formulatory agents, such as, suspending, stabilizing and/or dispersing agents. Alternatively, the pharmaceutical compositions can be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization from solution, for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use. The pharmaceutical compositions can be formulated as an aqueous solution, an aqua- alcoholic solution, a solid suspension, an emulsion, a liposomal suspension, or a freeze-dried powder for reconstitution. Such pharmaceutical compositions can be administered directly or as an admixture for further dilution/reconstitution. Route of administration includes intravenous bolus, intravenous infusion, irrigation, and instillation. Aqueous formulations suitable for oral use can be prepared by dissolving or suspending the active component in water and adding suitable colorants, flavors, stabilizing, and thickening agents, as desired. Aqueous suspensions suitable for oral use can be made by dispersing the finely divided drug substance in water with viscous material. For topical administration to the epidermis the compounds described herein, or pharmaceutically acceptable salts thereof can be formulated as gels, ointments, creams, or lotions, or as a transdermal patch. Also, formulations suitable for topical administration in the mouth include lozenges comprising drug substance in a flavored base. Solutions or suspensions can be applied directly to the nasal cavity by conventional means, for example with a dropper, pipette, or spray. The formulations can be provided in single or multi- dose form. In the latter case of a dropper or pipette, this can be achieved by the patient administering an appropriate, predetermined volume of the solution or suspension. In the case of a spray, this can be achieved for example by means of a metering atomizing spray pump. Administration to the respiratory tract can also be achieved by means of an aerosol formulation provided in a pressurized pack with a suitable propellant. If the compounds described herein, or pharmaceutically acceptable salts thereof or pharmaceutical compositions comprising them are administered as aerosols, for example as nasal aerosols or by inhalation, this can be carried out, for example, using a spray, a nebulizer, a pump nebulizer, an inhalation apparatus, a metered inhaler, or a dry powder inhaler. Alternatively, the pharmaceutical composition can be provided in the form of a dry powder, for example, a powder mix of the compound in a suitable, powder base, such as, lactose, starch, starch derivatives. Conveniently the powder carrier will form a gel in the nasal cavity. The powder composition may be presented in unit dose form for example in capsules or cartridges of, e.g., gelatin, or blister packs from which the powder may be administered by means of an inhaler. The compounds, as described herein, or pharmaceutically acceptable salts thereof, can also be administered via a rapid dissolving or a slow-release composition, wherein the composition includes a biodegradable rapid dissolving or slow-release carrier. The pharmaceutical preparations are preferably in unit dosage forms. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the drug substance. The unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as, packeted tablets, capsules, and powders in vials or ampoules. Also, the unit dosage form can be a capsule, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form. In some embodiments, the pharmaceutical preparation is a tablet or capsule for oral administration. In some embodiments, the pharmaceutical preparation is a liquid formulated for intravenous administration. The compositions can be formulated in a unit dosage form, each dosage containing the drug substance or equivalent mass of the drug substance. The term “unit dosage forms” refers to physically discrete units of a formulation suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable excipient, as described herein. The liquid forms including the drug substance can be incorporated for administration orally or by injection include aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils. The pharmaceutical compositions described herein can be sterilized by conventional sterilization techniques, or can be sterile filtered. Aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous carrier prior to administration. Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous, or organic solvents, or mixtures thereof, and powders. The liquid or solid compositions may contain suitable excipients as described herein. In some embodiments, the compositions are administered by the oral or nasal respiratory route for local or systemic effect. Compositions can be nebulized by use of inert gases. Nebulized solutions may be breathed directly from the nebulizing device, or the nebulizing device can be attached to a face masks tent, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions can be administered orally or nasally from devices which deliver the formulation in an appropriate manner. The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more-unit dosage forms containing the drug substance. The pack may for example comprise metal or plastic foil, such as, a blister pack. The pack or dispenser device can be accompanied by instructions for administration. The pack or dispenser may also be accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration. Such notice, for example, can be the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product insert. Compositions that can include a compound described herein formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition. For preparing solid compositions, such as, tablets, the drug substance can be mixed with an excipient to form a solid preformulation composition containing a homogeneous mixture of components. When referring to these preformulation compositions as homogeneous, the drug substance is typically dispersed evenly throughout the composition so that the composition can be readily subdivided into equally effective unit dosage forms, such as, tablets and capsules. Kits with unit doses of one or more of the compounds described herein, or a pharmaceutically acceptable salt thereof, usually in oral or injectable doses, are provided. Such kits can include a container containing the unit dose, an informational package insert describing the use and attendant benefits of the drugs in treating pathological condition of interest, and optionally an appliance or device for delivery of the composition. The compounds described herein, or a pharmaceutically acceptable salt thereof, can be effective over a wide dosage range and are generally administered in a therapeutically effective amount. It will be understood, however, that the amount of the compound actually administered will usually be determined by a physician, according to the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered, the age, weight, and response of the individual subject, the severity of the subject’s symptoms, and the like. The amount of compound or composition administered to a subject will also vary depending upon what is being administered, the purpose of the administration, such as, prophylaxis or therapy, the state of the subject, the manner of administration, and the like. In therapeutic applications, compositions can be administered to a subject already suffering from a disease in an amount sufficient to cure or at least partially arrest the symptomology and/or pathology of the disease and its complications. Therapeutically effective doses will depend on the disease condition being treated as well as by the judgment of the attending clinician depending upon factors, such as, the severity of the disease, the age, weight, and general condition of the subject, and the like. The desired dose may conveniently be presented in a single dose or presented as divided doses administered at appropriate intervals, for example, as two, three, four, or more sub-doses per day. The sub-dose itself can be further divided, e.g., into a number of discrete loosely spaced administrations. The daily dose can be divided, especially when relatively large amounts are administered as deemed appropriate, into several, for example two, three, or four-part administrations. If appropriate, depending on individual behavior, it can be necessary to deviate upward or downward from the daily dose indicated. It will be apparent to those skilled in the art that the dosage forms described herein can comprise a compound described herein or pharmaceutically acceptable salt thereof. PREPARATIONS As used herein, a “preparation” is the product of a process used to make or isolate a compound as disclosed and described herein, wherein the preparation contains at least one other component in addition to the compound. In some embodiments, the preparation comprises a chemical entity. As used herein, a “chemical entity” defined in the context of a “preparation,” refers to a compound as disclosed and described herein and at least one other component in addition to the compound. For example, a chemical entity can be a co-crystal or salt of a compound as disclosed and described herein. Some embodiments provide a preparation comprising a compound as disclosed and described herein. In some embodiments, the compound is a component of a chemical entity. In some embodiments, the chemical entity is a salt of a compound as disclosed and described herein. In some embodiments, the chemical entity is a (2S,3S)-2,3-bis(4-methylbenzoyloxy)butanedioic acid (DPTTA) salt of a compound as disclosed and described herein. In some embodiments, the compound of the preparation is in at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, 99.5%, 99.9%, or 100% enantiomeric excess, or an enantiomeric excess within a range defined by any of the preceding numbers. In some embodiments, the compound of the preparation is in at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% enantiomeric excess, or an enantiomeric excess within a range defined by any of the preceding numbers. In some embodiments, the compound of the preparation is in at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 99.9% diastereomeric excess, or a diastereomeric excess within a range defined by any of the preceding numbers. In some embodiments, the compound of the preparation is in at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% diastereomeric excess, or a diastereomeric excess within a range defined by any of the preceding numbers. In some embodiments, the preparation comprises at least 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 93% by weight of the compound, or a % by weight within a range defined by any of the preceding numbers. In some embodiments, the preparation comprises at least 50%, 60%, 70%, 80%, 90%, or 93% by weight of the compound, or a % by weight within a range defined by any of the preceding numbers. In some embodiments, the preparation comprises at most 50%, 60%, 70%, 80%, 90%, 93%, or 95% by weight of the compound, or a % by weight within a range defined by any of the preceding numbers. In some embodiments, the preparation comprises at least 50% by weight of the compound. In some embodiments, the preparation is in the form of a solid, i.e., a solid preparation. In some embodiments, the preparation is used to prepare a pharmaceutical composition. METHODS OF USE The compounds, as described herein, are inhibitors of VMAT2. Accordingly, the present disclosure includes a method of inhibiting VMAT2 (i.e., decreasing at least one function of VMAT2 or decreasing expression of VMAT2) by contacting the VMAT2 with a compound as disclosed and described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the contacting can occur in vitro, such as, where the VMAT2 is located in a purified preparation or in a cell outside of a living organism (e.g., in a tissue sample or a cellular preparation). In some embodiments, the contacting can occur in vivo, such as, where the VMAT2 is located in a living organism. The VMAT2 inhibitors described herein can reduce the level of monoamines in the central nervous system. Accordingly, the present disclosure includes a method of reducing the level of monoamines in the central nervous system of a subject comprising administering to the subject an amount of a compound, as described herein, or a pharmaceutically acceptable salt thereof, sufficient to lower the level of monoamines relative to the level prior to administration. The VMAT2 inhibitors as disclosed and described herein are believed to have utility over a wide range of therapeutic applications, and may be used to treat or prevent a variety of disorders which are caused by or linked to inhibition of the human vesicular monoamine transporter isoform 2. These disorders include neurological and psychiatric disorders, for example, hyperkinetic movement disorders, schizophrenia, and mood disorders. A compound, as described herein, or a pharmaceutically acceptable salt thereof, can be used in any of the therapeutic methods disclosed and described herein. Accordingly, in various embodiments as disclosed herein, methods are provided for treating or preventing a neurological and/or psychiatric disease or disorder in a subject in need thereof by administering to the subject a pharmaceutically effective amount of a VMAT2 inhibitor as described herein, or a pharmaceutically acceptable salt thereof. The neurological and/or psychiatric disease or disorder can be, for example, a hyperkinetic movement disorder, schizophrenia, schizoaffective disorder, a mood disorder, treatment-refractory obsessive-compulsive disorder, neurological dysfunction associated with Lesch-Nyhan syndrome, agitation associated with Alzheimer’s disease, Fragile X syndrome or Fragile X-associated tremor-ataxia syndrome, autism spectrum disorder (e.g., restricted and repetitive behaviors associated with Autism spectrum disorder (ASD)), Rett syndrome, or chorea-acanthocytosis. In various other embodiments as disclosed herein, methods are provided for treating or preventing a vesicular monoamine transporter-2 (VMAT2) disease or disorder in a subject in need thereof by administering to the subject a pharmaceutically effective amount of a VMAT2 inhibitor as described herein, or a pharmaceutically acceptable salt thereof. The VMAT2 disease or disorder can be, for example, an ataxias or spinal muscular atrophy; a chorea; a congenital malformation, deformation, or abnormality; a dementia; an oral cavity, salivary gland, or jaw disease; a dyskinesia; a dystonia; an endocrine, nutritional, or metabolic disease; an epilepsy; a habit or impulse disorder; a Huntington’s disease or related disorder; a mood or psychotic disorder; a neurotic, stress-related, and somatoform disorder; a degenerative disease of the basal ganglia; an extrapyramidal and movement disorder; a neurological or psychiatric disease or disorder; a nervous system or motor function disorder; a Parkinson’s/parkinsonism disorder; a pediatric-onset behavioral and emotional disorder; a pervasive developmental disorder; and a substance abuse or dependence disorder. Accordingly, in various embodiments as disclosed herein, methods are provided for treating or preventing a hyperkinetic movement disorder in a subject in need thereof by administering to the subject in need thereof a pharmaceutically effective amount of a VMAT2 inhibitor described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the hyperkinetic movement disorder is tardive dyskinesia, Tourette's syndrome, Huntington's disease, chorea associated with Huntington’s disease, or tics. In other embodiments, the hyperkinetic movement disorder is ataxia, chorea, dystonia, hemifacial spasm, myoclonus, restless leg syndrome, or tremors. In some embodiments, methods are provided for treating or preventing a mood disorder in a subject in need thereof by administering to the subject in need thereof a pharmaceutically effective amount of a VMAT2 inhibitor described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the mood disorder is bipolar disorder, major depressive disorder, mania in a mood disorder, or depression in a mood disorder. In some embodiments as disclosed herein, methods are provided for treating or preventing schizophrenia or schizoaffective disorder in a subject in need thereof by administering to the subject in need thereof a pharmaceutically effective amount of a VMAT2 inhibitor described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the neurological or psychiatric disease or disorder is a hyperkinetic movement disorder. In some embodiments, the hyperkinetic movement disorder is tardive dyskinesia. In some embodiments, the hyperkinetic movement disorder is Tourette's syndrome. In some embodiments, the hyperkinetic movement disorder is Huntington's disease. In some embodiments, the hyperkinetic movement disorder is tics. In some embodiments, the hyperkinetic movement disorder is chorea associated with Huntington's disease. In some embodiments, the hyperkinetic movement disorder is ataxia, chorea, dystonia, hemifacial spasm, Huntington's disease, myoclonus, restless leg syndrome, or tremors. In some embodiments, the neurological or psychiatric disease or disorder is selected from schizophrenia and schizoaffective disorder. In some embodiments, the neurological or psychiatric disease or disorder is schizophrenia. In some embodiments, the neurological or psychiatric disease or disorder is schizoaffective disorder. In some embodiments, the neurological or psychiatric disease or disorder is obsessive- compulsive disorder. In some embodiments, the neurological or psychiatric disease or disorder is treatment- refractory obsessive-compulsive disorder. In some embodiments, the neurological or psychiatric disease or disorder is autism spectrum disorder. In some embodiments, the neurological or psychiatric disease or disorder is restricted and repetitive behaviors associated with Autism spectrum disorder (ASD). In some embodiments, the neurological or psychiatric disease or disorder is obsessions and compulsions in partial and non-responders (or completely refractory) with obsessive-compulsive disorder (OCD). In some embodiments, the neurological or psychiatric disease or disorder is obsessions and compulsions in partial and non-responders (or completely refractory) with obsessive- compulsive disorder (OCD) and the compounds described herein are administered as adjunctive therapy. In some embodiments, compounds described herein are useful as an adjunctive therapy or adjunctive treatment of schizophrenia. In some embodiments, the compounds described here are administered as adjunctive therapy with the primary therapy being treatment with antidepressants. In some embodiments, the neurological or psychiatric disease or disorder is Bipolar I Disorder. In some embodiments, the compound described herein is administered as monotherapy for the treatment of Bipolar I Disorder. In some embodiments, the compound described herein is administered as maintenance therapy for the treatment of Bipolar I Disorder. In some embodiments, the compound described herein is administered as monotherapy maintenance therapy for the treatment of Bipolar I Disorder. In some embodiments, the compound, as described herein, or a pharmaceutically acceptable salt thereof, is administered to the patient to treat or prevent a disease or disorder selected from: ataxias or spinal muscular atrophies, such as, spinocerebellar ataxia type 17 (SCA17) / HDL4, ataxia, spinal muscular atrophy, amyotrophic lateral sclerosis, familial amyotrophic lateral sclerosis, bulbospinal muscular atrophy congenital, dentatorubral-pallidoluysian atrophy, hereditary motor neuron disease, and hereditary spastic paraplegia; chorea, such as, benign hereditary chorea, chorea, chorea associated with mitochondrial disease/causes, chorea associated with Wilson's disease, chorea gravidarum, chorea-acanthocytosis, drug-induced chorea, hemiballism, rheumatic/Sydenham's chorea, and thyrotoxic chorea/hyperthyroid chorea; congenital malformations, deformations, or abnormalities, such as, Angelman syndrome, congenital neurological disorder, Aicardi’s syndrome, neurofibromatosis, congenital facial nerve hypoplasia, Moebius II syndrome, Cockayne’s syndrome, Sjogren-Larsson syndrome, Laurence- Moon-Bardet-Biedl syndrome, Fragile X syndrome, and Prader-Willi syndrome; dementia, such as, AIDS-related dementia, Alzheimer's disease, congenital neurological degeneration, Lewy body dementia, micro-infarct dementia, pre-senile dementia, senile dementia, and vascular dementia; diseases of oral cavity, salivary glands, and jaws, such as, glossodynia / burning mouth syndrome and temporomandibular joint disorder; dyskinesia, such as, pharyngeal dyskinesia, dyskinesia, dyskinesia (neonatal), dyskinesia (oesophageal), levodopa-induced dyskinesia, paroxysmal kinesigenic dyskinesias, paroxysmal nonkinesigneic dyskinesias, and respiratory dyskinesia; dystonia, such as, blepharospasm, buccoglossal syndrome, drug-induced acute dystonia, dystonia, early onset primary dystonia, genetic torsion dystonia, hand dystonia/writer's cramp, idiopathic nonfamilial dystonia, idiopathic orofacial dystonia/Meige's disease, laryngeal dystonia, oromandibular dystonia, and spasmodic torticollis/cervical dystonia; endocrine, nutritional, and metabolic diseases, such as, Wilson’s Disease, diabetes mellitus, obesity, syndrome X, and Lesch-Nyhan syndromes; epilepsy, such as, Baltic myoclonic epilepsy, benign familial neonatal convulsions, epilepsy, epilepsy congenital, Lafora’s myoclonic epilepsy, severe myoclonic epilepsy of infancy, and convulsions; habit and impulse disorders, such as, binge eating disorder, kleptomania, impulse control disorders, trichotillomania, intermittent explosive disorder, pathological gambling, and pyromania; Huntington’s disease or related disorders, such as, Huntington’s disease, Huntington's disease-like syndromes 1-3, Huntington's chorea, and X-linked McLeod Neuroacanthocytosis syndrome; mood or psychotic disorders, such as, schizophrenia, psychosis, mania, bipolar disorder, depression, and mood disorders; other diseases or disorders, such as, fumbling, hypokinesia, hypokinesia (neonatal), movement disorder, rabbit syndrome, spasticity, up and down phenomenon, asthma, cancer, congenital nystagmus, familial hemiplegic migraine, fetal movement disorder, and rheumatoid arthritis; neurotic, stress-related, and somatoform disorders, such as, social anxiety disorder, panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, post-traumatic stress disorder, and psychogenic movement disorder; other degenerative diseases of basal ganglia, such as, pantothenate kinase-associated neurodegeneration, progressive supranuclear palsy, multiple system atrophy, dyslexia, basal ganglion degeneration, and neuroferritinopathy; other extrapyramidal and movement disorders, such as, hemiballismus, extrapyramidal disorder, essential tremor, geniospasm, hyperexplexia, akathisia, ballismus / hemiballism, myoclonus, and restless legs syndrome / Willis-Ekbom's syndrome; other nervous system or motor function, such as, sleep-related bruxism, abnormal involuntary movement disorders, alien limb syndrome, Alzheimer's disease (agitation), clumsiness, clonic hemifacial spasm, olfactory nerve agenesis, congenital cranial nerve paralysis, exercise ataxia syndrome, familial periodic paralysis, congenital hemiparesis, fine motor delay, fine motor skill dysfunction, gross motor delay, multiple sclerosis, congenital flaccid paralysis, congenital Horner’s syndrome, alternating hemiplegia of childhood, motor developmental delay, cerebral palsy, athetoid cerebral palsy, posturing, pseudoparalysis, psychomotor hyperactivity, bradykinesia, synkinesis, akinesia, Riley-Day syndrome, and athetosis; Parkinson’s/parkinsonism, such as, parkinsonism, drug-induced parkinsonism, micrographia, and Parkinson's disease; pediatric-onset behavioral and emotional disorders, such as, attention deficit hyperactivity disorder, attention deficit disorder, hyperkinesia, hyperkinesia (neonatal), oppositional defiant disorder, provisional tic disorder, persistent (chronic) motor or vocal tic disorder, stereotypic movement disorder, stereotypy, and Tourette's syndrome; pervasive developmental disorders, such as, autism spectrum disorders, Rett's syndrome, Asperger's syndrome, pervasive developmental disorder NOS, and dyslexia; and substance abuse or dependence, such as, addiction disorders, alcoholism, cocaine dependence, illegal drug abuse, methamphetamine abuse, methamphetamine addiction/dependence, methamphetamine use disorder, morphine abuse, morphine-analogue abuse, nicotine dependence, polysubstance abuse, and prescription drug abuse. In some embodiments, the compound, as described herein, or a pharmaceutically acceptable salt thereof, is administered to the patient to treat or prevent a palsy. In some embodiments, the palsy is selected from: spastic cerebral palsy (including, but not limited to, spastic hemiplegia cerebral palsy, spastic diplegia cerebral palsy, and spastic quadriplegia cerebral palsy), dyskinetic cerebral palsy, ataxic cerebral palsy, and “mixed types” cerebral palsy. In some embodiments, the palsy is spastic cerebral palsy. In some embodiments, the palsy is dyskinetic cerebral palsy. In some embodiments, the palsy is ataxic cerebral palsy. In some embodiments, the palsy is “mixed types” cerebral palsy. The phrase “mixed types” cerebral palsy includes a mix of symptoms associated with other types of cerebral palsies. In some embodiments, the patient which is treated has been determined to have 22q11.2 deletion syndrome. In some embodiments, the patient is predisposed to developing a psychiatric disorder due to the patient having 22q11.2 deletion syndrome. In some embodiments, the patient has been determined to have COMT haploinsufficiency. In some embodiments, the patient is predisposed to developing a psychiatric disorder due to the patient having COMT haploinsufficiency. In another embodiment, the VMAT2 inhibitors described herein may be hydrolyzed in the body of a mammal to compounds that may inhibit the human vesicular monoamine transporter isoform 2. As such, these VMAT2 inhibitors may have additional utility in altering the in vivo properties of the metabolite in a mammal, such as, the maximum concentration or duration of action. Characterizing any of the VMAT2 inhibitors described herein may be determined using methods described herein, and those in the art. For example, dopamine depletion may be determined using the locomotor activity (LMA) assay. Another in vivo animal model includes the conditioned avoidance response (CAR) test, which has been shown to be an effective and reliable preclinical model for assessing the antipsychotic activity of compounds. COMBINATION THERAPY The compounds of the present disclosure, and their pharmaceutically acceptable salts, can be used as monotherapy, or in combination with one or more other pharmaceutical agents. In some embodiments, a compound, as described herein, or its pharmaceutically acceptable salt, is administered together with (simultaneously or sequentially) one or more pharmaceutical agents selected from antidepressants, antipsychotics (typical or atypical), antiepileptics, antimicrobials, antiarrhythmics, mood stabilizers, and gastrointestinal drugs. In some embodiments, a compound, as described herein, or a pharmaceutically acceptable salt thereof, is used in adjunctive therapy which refers to a treatment that is used in conjunction with a primary treatment and its purpose is to assist the primary treatment. Adjunctive therapies are typically co-administered therapies. As an example of adjunctive therapy, if obsessive-compulsive disorder is being treated, the primary therapy may be, e.g., an antidepressant, and the co-administration of a compound described herein would be considered an adjunctive therapy. COMPOUND SYNTHESIS Detailed compound synthesis methods are described herein in the Examples. In general, starting components are commercially available chemicals and may be obtained from commercial sources or may be made according to organic synthesis techniques known to those skilled in this art, starting from commercially available chemicals and/or from compounds described in the chemical literature. In general, the compounds used in the reactions described herein may be made according to organic synthesis techniques known to those skilled in this art, starting from commercially available chemicals and/or from compounds described in the chemical literature. Methods known to one of ordinary skill in the art may be identified through various reference books and databases. Suitable reference books and treatise that detail the synthesis of reactants useful in the preparation of compounds of the present disclosure, or provide references to articles that describe the preparation, include for example, “Synthetic Organic Chemistry,” John Wiley & Sons, Inc., New York; S. R. Sandler et al., “Organic Functional Group Preparations,” 2nd Ed., Academic Press, New York, 1983; H. O. House, “Modern Synthetic Reactions”, 2nd Ed., W. A. Benjamin, Inc. Menlo Park, Calif.1972; T. L. Gilchrist, “Heterocyclic Chemistry”, 2nd Ed., John Wiley & Sons, New York, 1992; J. March, “Advanced Organic Chemistry: Reactions, Mechanisms and Structure,” 4th Ed., Wiley-Interscience, New York, 1992. Specific and analogous reactants may also be identified through the indices of known chemicals prepared by the Chemical Abstract Service of the American Chemical Society, which are available in most public and university libraries, as well as through on-line databases (the American Chemical Society, Washington, D.C., may be contacted for more details). Chemicals that are known but not commercially available in catalogs may be prepared by custom chemical synthesis houses according to known methods, where many of the standard chemical supply houses (e.g., those listed above) provide custom synthesis services. EXAMPLES The following examples are included to demonstrate embodiments of the disclosure. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the disclosure. Additional illustrated syntheses for compounds of the present invention are shown in the accompanying Figures where the symbols have the same definitions as used throughout this disclosure. Analytical HPLC analyses were performed on an LC-MS system with a UV Detector (Dionex ^TM UVD 170u UV/VIS Detector), Corona array detector (Thermo ^TM Veo ^TM RS), and mass spectrometer (Dionex MSQ Plus ^TM ). Reverse-phase preparative HPLC purifications were performed on a liquid chromatography-mass spectrometry (LCMS) system C ₁₈ Kinetix 5μ 100 A 150 x 21.2 mm column by Phenomenex using ACN/water gradient containing 0.05% TFA. Supercritical fluid chromatography purification (SFC) was performed using a Waters ^TM Prep 100q ^TM system, equipped with a UV Detector (Waters ^TM 2998 Photodiode Array Detector ^TM ) and mass spectrometer (Waters ^TM Acquity QDa Detector ^TM ). A Waters ^TM Viridis ^TM BEH 2-Ethylpyridine 130 Å 5 µm, 30 mm x 100 mm column was used with a CO2 and 0.3% NH ₄ OH in MeOH gradient, run at 100 mL/min, 40°C, and 105 bar back pressure regulator. All final compounds were analyzed by analytical HPLC, and peaks were monitored at 210, 254, and 280 nm for purity. ¹ H was recorded in an appropriate NMR solvent, such as, dimethylsulfoxide-d ₆ (DMSO-d ₆ ), on a Bruker 400 MHz spectrometer equipped with a Broad Band NMR probe, or on a Bruker 500 MHz spectrometer equipped with a 5 mm QNP probe with Z gradient. The ¹ H chemical signals are given in parts per million (ppm) with the residual solvent signal used as reference. The chemical shifts are expressed in ppm (δ) and coupling constants (J) are reported in hertz (Hz). Reactions were performed under an atmosphere of dry nitrogen unless otherwise stated. EXAMPLE 1: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 15); (2S,3R,11bR)-3-(tert-butoxy)-9,10- dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoli n-2-ol (Compound 76); (2S,3S,11bS)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 77); and (2R,3S,11bS)-3-(tert-butoxy)-9,10-dimethoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 78). Step 1: Preparation of N,N,N-trimethyl-3-oxobutan-1-aminium iodide (Compound 2-2). To a solution of 4-(dimethylamino)butan-2-one (Compound 2-1, 15.0 g, 130 mmol, 1.0 eq) in EtOAc (260 mL) was added methyl iodide (55.4 g, 390 mmol, 3.0 eq) and the mixture was stirred overnight at room temperature (RT). The mixture was concentrated in vacuo to give crude N,N,N- trimethyl-3-oxobutan-1-aminium iodide (Compound 2-2, 31.51 g, 123 mmol, 94%) as a light red solid that was used without further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 3.50 (t, J = 7.5 Hz, 2H), 3.12 - 3.09 (t, J = 7.0 Hz, 2H), 3.04 (s, 9H), 2.18 (s, 3H). Step 2: Preparation of (±)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-one (Compound 2-4). To a solution of 6,7-dimethoxy-3,4-dihydroisoquinoline (Compound 2-3, 6.60 g, 34.5 mmol, 1.0 eq) in MeOH (66 mL) was added N,N,N-trimethyl-3-oxobutan-1-aminium iodide (Compound 2- 2, 13.3 g, 51.8 mmol, 1.5 eq) and the mixture was stirred at reflux for 1h. The mixture was cooled to RT and stirred 1h. The mixture was concentrated in vacuo, suspended in water, and extracted three times with DCM. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude material was submitted to two chromatographic separations: a silica gel column (220 g) loaded using DCM run with an increasing gradient of MeOH (0-5% over 20 min) in DCM and the mixed fractions further purified with a silica gel column (40 g) loaded using DCM run with an increasing gradient of EtOAc (0-100% over 20 min) in hexanes to afford (±)-9,10-dimethoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one (Compound 2-4, 6.89 g, 26.4 mmol, 77%) as an off-white solid. ¹ H NMR (400 MHz, DMSO-d6): δ (ppm) 6.71 (s, 1H), 6.70 (s, 1H), 3.72 (s, 6H), 3.46 (br d, J = 11.1 Hz, 1H), 3.25 - 3.16 (m, 1H), 3.14 - 3.05 (m, 1H), 2.98 - 2.83 (m, 2H), 2.71 - 2.56 (m, 3H), 2.49 - 2.42 (m, 1H), 2.34 (dd, J = 12.0, 14.2 Hz, 1H), 2.23 (br d, J = 11.2 Hz, 1H). Step 3: Preparation of (±)-3-((dimethylamino)methylene)-9,10-dimethoxy-1,3,4,6,7,1 1b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one (Compound 2-5). To a solution of (±)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a] isoquinolin-2- one (Compound 2-4, 4.40 g, 16.8 mmol, 1.0 eq) in THF (44 mL) was added 1-tert-butoxy-N,N,N',N'- tetramethylmethanediamine (3.52 g, 20.2 mmol, 1.2 eq) and the mixture was stirred at reflux overnight. The mixture was cooled to RT and diluted with water (40 mL) and aq. HCl (1 M, 50.5 mL, 50.5 mmol, 3.0 eq) and stirred 1h. The reaction was quenched with saturated aq. NaHCO ₃ and extracted three times with 5:1 DCM:i-PrOH. The aqueous layer was adjusted to pH = 7 and extracted three times with 5:1 DCM:i-PrOH. The organic layers were discarded. The aqueous layer was concentrated in vacuo then placed under vacuum overnight to afford (±)-3- ((dimethylamino)methylene)-9,10-dimethoxy-1,3,4,6,7,11b-hexa hydro-2H-pyrido[2,1-a]isoquinolin- 2-one (Compound 2-5, 4.39 g, 13.9 mmol, 83%) as a sticky yellow solid that was carried on without further purification. Step 4: Preparation of (±)-sodium (9,10-dimethoxy-2-oxo-1,6,7,11b-tetrahydro-2H- pyrido[2,1-a]isoquinolin-3(4H)-ylidene)methanolate(Compound 2-6). To a solution of (±)-3-((dimethylamino)methylene)-9,10-dimethoxy-1,3,4,6,7,1 1b-hexahydro- 2H-pyrido[2,1-a]isoquinolin-2-one (Compound 2-5, 4.19 g, 13.2 mmol, 1.0 eq) in water (80 mL) was added aq. HCl (12.1 M, 2.7 mL, 33.0 mmol, 2.5 eq) at 0°C and stirred 30 min. The mixture was allowed to warm to RT and stir overnight. The reaction was quenched with saturated aq. NaHCO3 and extracted three times with EtOAc. The organic extracts were discarded. The aqueous layer was basified to pH = 11 with aq. NaOH (6 M). The aqueous layer was concentrated. The crude material was slurried in MeOH (50 mL). The solid precipitate was collected by vacuum filtration over celite. The filtrate was concentrated to afford crude (±)-sodium (9,10-dimethoxy-2-oxo-1,6,7,11b- tetrahydro-2H-pyrido[2,1-a]isoquinolin-3(4H)-ylidene)methano late (Compound 2-6, 5.61 g) as a solid, of which 2.10 g was taken directly to the next step (i.e., synthesis of (±)-3-diazo-9,10- dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoli n-2-one (Compound 2-7)). Step 5: Preparation of (±)-3-diazo-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-one (Compound 2-7). To a solution of crude sodium (±)- (9,10-dimethoxy-2-oxo-1,6,7,11b-tetrahydro-2H- pyrido[2,1-a]isoquinolin-3(4H)-ylidene)methanolate (Compound 2-6, 2.10 g) in DCM (6.5 mL) was added triethylamine (1.97 mL, 14.1 mmol). The mixture was cooled to 0°C prior to the addition of tosyl azide (1.27 g, 6.42 mmol). The reaction was stirred 1h at 0°C then allowed to warm to RT and stirred 2h. Aq. KOH (1.4 M, 4.81 mL, 6.74 mL) was added, and the reaction was stirred an additional 15 min. The mixture was extracted three times with DCM. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. A silica gel column (24 g) was loaded using DCM and run with an increasing gradient of EtOAc (0-100% over 12 min) in hexanes to afford (±)-3-diazo- 9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoqu inolin-2-one (Compound 2-7, 0.337 g, 1.17 mmol, 24% over two steps) as a brown solid. ¹ H NMR (500 MHz, DMSO-d ₆ ): δ (ppm) 6.75 (s, 1H), 6.68 (s, 1H), 4.01 (d, J = 12.6 Hz, 1H), 3.76 - 3.69 (m, 2H), 3.71 (s, 6H), 3.05 (td, J = 4.6, 11.1 Hz, 1H), 2.97 (dd, J = 4.1, 17.5 Hz, 1H), 2.88 - 2.81 (m, 1H), 2.68 (td, J = 4.0, 15.9 Hz, 1H), 2.53 (m, 1H), 2.14 (dd, J = 11.2, 17.5 Hz, 1H). Step 6: Preparation of (±)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro- 2H- pyrido[2,1-a]isoquinolin-2-one (Compound (±)-2-8). To a solution of (±)-3-diazo-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro-2H-pyrid o[2,1- a]isoquinolin-2-one (Compound 2-7, 0.140 g, 0.487 mmol, 1.0 eq) in tert-butanol (1.0 mL) was added dirhodium tetraacetate (10.8 mg, 0.0244 mmol, 0.050 eq). The mixture was heated at 80°C with stirring for 2h. The mixture was cooled to RT, filtered over celite, and concentrated in vacuo. A silica gel column (4 g) was loaded using DCM and run with an increasing gradient of EtOAc (0-50% over 20 min) in hexanes to afford (±)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro- 2H- pyrido[2,1-a]isoquinolin-2-one (Compound (±)-2-8, 0.027 g, 0.0810 mmol, 17%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ (ppm) 6.72 (s, 1H), 6.69 (s, 1H), 4.37 (dd, J = 6.8, 11.0 Hz, 1H), 3.72 (s, 6H), 3.46 (br d, J = 11.0 Hz, 1H), 3.21 - 3.10 (m, 2H), 2.96 - 2.84 (m, 2H), 2.72 - 2.64 (m, 1H), 2.58 - 2.42 (m, 3H), 1.15 (s, 9H). Step 7: Preparation of (±)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro- 2H- pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-9) and isolation of Compound 15, Compound 76, Compound 77, and Compound 78. To a solution of (±)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro- 2H-pyrido[2,1- a]isoquinolin-2-one (Compound (±)-2-8, 27 mg, 0.0810 mmol, 1.0 eq) in MeOH (2.0 mL) at 0°C was added NaBH4 (4.6 mg, 0.121 mmol, 1.5 eq). The mixture was warmed to RT and stirred overnight. The reaction mixture was quenched with water and extracted three times with DCM. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. A silica gel column (4 g) was loaded using DCM and run with an increasing gradient of EtOAc (0-100% over 20 min) in hexanes to afford (±)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-hexahydro- 2H- pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-9, 22 mg, 0.066 mmol, 81%) as a mixture of diastereomers. Separation of the resulting four isomers was achieved by preparing a solution in a minimal volume of MeOH and subjecting to preparative chiral SFC. Chiral compound separation was performed using a Pic Solution ^TM SFC-PICLAB-Prep 200 ^TM supercritical fluid chromatography (SFC) system, equipped with a UV Detector and an Advion ^TM mass spectrometer. A Chiral Technologies Inc ^TM ChiralPak ^TM IG/SFC 5 µm, 20 mm x 250 mm column was used with an isocratic gradient at 85% CO ₂ and 15% 0.5% DMEA in MeOH, at 150 mL/min, 55°C, and 110 bar back pressure regulator. The following quantities of Compound 15, Compound 76, Compound 77, and Compound 78 were obtained: (2R,3R,11bR)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 15, 6 mg, 0.0179 mmol, 22%, latest retention time of four isomers); (2S,3R,11bR)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 76, 3 mg, 0.00894 mmol, 11%, earliest retention time of four isomers); (2S,3S,11bS)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 77, 6 mg, 0.0179 mmol, 22%, second earliest retention time of four isomers); (2R,3S,11bS)-3-(tert-butoxy)-9,10-dimethoxy-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 78, 4 mg, 0.0119 mmol, 15%, second latest retention time of four isomers). EXAMPLE 2: Preparation of (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 2-21). Step 1: Preparation of 4-(tert-butoxy)-3-oxobutanoic acid (Compound 2-15). To a mixture of ethyl 4-(tert-butoxy)-3-oxobutanoate (Compound 2-14, 39.4 g, 195 mmol, 1.0 eq) and water (600 mL) was added aq. NaOH (6 N, 68.3 mL, 410 mmol, 2.1 eq) and the resulting mixture stirred at RT overnight. The mixture was cooled to 0°C then acidified with concentrated H ₂ SO ₄ to pH 1-2. The aqueous layer was extracted five times with MTBE. The combined organic extracts were dried over MgSO ₄ , filtered, and concentrated in vacuo to afford crude 4-(tert-butoxy)-3- oxobutanoic acid (Compound 2-15, 33.1 g 190 mmol, 97%) as a clear brown oil that was carried on without any further purification. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 12.53 (bs, 1H), 4.05 (s, 2H), 3.43 (s, 2H), 1.14 (s, 9H). Step 2: Preparation of (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one (Compound (±)-2-18). To a solution of 6-(benzyloxy)-7-methoxy-3,4-dihydroisoquinoline hydrochloride (Compound 2-16, 28.9 g, 95 mmol, 1.0 eq) in water (289 mL) was added NaOAc (0.779 g, 9.50 mmol, 0.1 eq) at 50°C. A solution of 4-(tert-butoxy)-3-oxobutanoic acid (Compound 2-15, 33.1 g, 190 mmol, 2.0 eq) was added dropwise and the mixture was stirred at 50°C for 3h. The mixture was cooled to RT and quenched with saturated aq. NaHCO3. The aqueous layer was extracted three times with MTBE. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo to afford crude (±)-1-(6-(benzyloxy)-7-methoxy-1,2,3,4-tetrahydroisoquinoli n-1-yl)-3-(tert- butoxy)propan-2-one (Compound 2-17) as a brown oil. To a solution of the crude material in MeOH (378 mL) was added acetic acid (5.4 mL, 95 mmol, 1.0 eq) and 37% (w/w) aq. formaldehyde (6.6 mL, 80.8 mmol, 0.85 eq). The mixture was stirred at 40°C overnight. The mixture was cooled to RT, quenched with saturated aq. NaHCO3, and extracted three times with DCM. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. Two silica gel columns (330 g) were loaded using DCM and run with an increasing gradient of EtOAc (0-50% over 20 min) in hexanes to afford (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H- pyrido[2,1-a]isoquinolin-2-one (Compound (±)-2-18, 13.1 g, 32.0 mmol, 34% over two steps) as an off white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.46 - 7.31 (m, 5H), 6.81 (s, 1H), 6.75 (s, 1H), 5.03 (s, 2H), 4.37 (dd, J = 7.0, 10.9 Hz, 1H), 3.74 (s, 3H), 3.46 (br d, J = 11.9 Hz, 1H), 3.23 - 3.09 (m, 2H), 2.95 - 2.84 (m, 2H), 2.70 - 2.62 (m, 1H), 2.59 - 2.42 (m, 3H), 1.15 (s, 9H). (Reduction, Method A) Step 3A: Preparation of (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-19). To a solution of 9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexah ydro-2H- pyrido[2,1-a]isoquinolin-2-one (Compound (±)-2-18, 10.9 g, 26.6 mmol, 1.0 eq) in MeOH (110 mL) at 0°C was added NaBH4 (2.01 g, 53.2 mmol, 2.0 eq) in portions. The mixture was stirred 30 min then warmed to RT and stirred 1h. The reaction mixture was diluted with water (100 mL) and aq. NaOH (1M, 100 mL) then extracted three times with DCM. The combined organic extracts were dried over MgSO ₄ , filtered, and concentrated in vacuo. A silica gel column (220 g) was loaded using DCM and run with an increasing gradient of EtOAc (0-80% over 20 min) in hexanes to afford (±)-9- (benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-19) as a 1.4:1 mixture of diastereomers (8.64 g, 21.0 mmol, 79%). (Reduction, Method B) Step 3B: Preparation of (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-19). To a solution of 9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexah ydro-2H- pyrido[2,1-a]isoquinolin-2-one (Compound (±)-2-18, 11.7 g, 28.5 mmol, 1.0 eq) in THF (184 mL) at 0°C was added DIBAL-H (1.0 M in hexanes, 42.8 mL, 42.8 mmol, 1.5 eq) dropwise. The mixture was stirred 1h at 0°C. The reaction mixture was quenched with acetone. The mixture was diluted with aq. Rochelle’s salt (10% w/w) and stirred vigorously for 30 min. The mixture was extracted three times with DCM. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo to afford crude (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-19) as a 6.5:1 mixture of diastereomers (11.70 g, 28.4 mmol, 99%) that was carried on directly to the next step (i.e., synthesis of (2R,3R,11bR)-9- (benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin-2-ol). Step 3C: Preparation of (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-20). Diastereomerically pure Compound (±)-2-20 could be obtained by chromatography of Compound (±)-2-19 (0.432 g, 1.05 mmol, 1.4:1 dr). A silica gel column (4 g) was loaded using DCM and run with an increasing gradient of EtOAc (0-100% over 20 min) in hexanes to afford (±)-9- (benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-20, 166 mg, 0.403 mmol, 38%). ¹ H NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.45 - 7.41 (m, 2H), 7.41 - 7.37 (m, 2H), 7.34 - 7.31 (m, 1H), 6.77 (s, 1H), 6.74 (s, 1H), 5.01 (s, 2H), 4.61 (d, J = 4.7 Hz, 1H), 3.73 (s, 3H), 3.32 - 3.27 (m, 2H), 3.02 (br d, J = 11.0 Hz, 1H), 2.92 - 2.82 (m, 3H), 2.54 - 2.45 (m, 2H), 2.35 - 2.29 (m, 1H), 2.04 (br t, J = 10.3 Hz, 1H), 1.27 - 1.21 (m, 1H), 1.17 (s, 9H). Step 4: Preparation of (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 2-21). To a solution of crude (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-19, 6.5:1 dr, 11.70 g, 28.5 mmol, 1 eq) in EtOH (250 mL) was added (2S,3S)-2,3-bis(4-methylbenzoyloxy)butanedioic acid (DPTTA, 11.00 g, 28.5 mmol, 1.0 eq). The solution was heated to reflux with stirring which became a suspension upon heating. After the addition of MeOH (60 mL) the mixture was held at reflux until a clear solution was obtained. The solution was cooled to 75°C, then seeded with Compound 2- 21·DPTTA (0.050 g, see Example 3 below) and held at constant temperature for 1h 30 min. The mixture was cooled at a rate of 8°C per h to RT, then continued stirring for two days. The resulting precipitate was collected by vacuum filtration and dried to provide Compound 2-21·DPTTA (7.357 g, 6.26 mmol, 32% over two steps from Compound (±)-2-18, prepared in Example 2, Step 2 above) as a white solid. An optical purity of 100% ee was determined by chiral supercritical fluid chromatography (SFC) analysis and a diastereomeric purity ≥ 99%. The chiral salt pair was suspended in DCM and water was added. The mixture was basified with saturated aq. NH ₄ OH until pH ~ 10. The mixture was extracted three times with DCM. The organic extracts were dried over MgSO ₄ , filtered, and concentrated in vacuo to afford the title compound (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)- 10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinol in-2-ol (Compound 2-21, 3.78 g, 6.12 mmol, 32% over two steps from Compound (±)-2-18, prepared in Example 2, Step 2 above) as a white solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 7.45 - 7.41 (m, 2H), 7.41 - 7.37 (m, 2H), 7.34 - 7.31 (m, 1H), 6.77 (s, 1H), 6.74 (s, 1H), 5.01 (s, 2H), 4.61 (d, J = 4.7 Hz, 1H), 3.73 (s, 3H), 3.32 - 3.27 (m, 2H), 3.02 (br d, J = 11.0 Hz, 1H), 2.92 - 2.82 (m, 3H), 2.54 - 2.45 (m, 2H), 2.35 - 2.29 (m, 1H), 2.04 (br t, J = 10.3 Hz, 1H), 1.27 - 1.21 (m, 1H), 1.17 (s, 9H). EXAMPLE 3: Preparation of the salt of (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol and (2S,3S)-2,3-bis(4- methylbenzoyloxy)butanedioic acid (Compound 2-21·DPTTA). To a solution of (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-20, 0.166 g, 0.403 mmol, 1.0 eq) in MeOH (2 mL) was added (2S,3S)-2,3-bis(4-methylbenzoyloxy)butanedioic acid (DPTTA, 0.156 g, 0.403 mmol, 1.0 eq). The mixture was heated to 50°C with stirring and held at that temperature for 10 min. The mixture was cooled to rt then concentrated in vacuo to give an off-white solid. The salt pair was suspended in EtOH (4 mL) and heated with stirring to 70°C to give a suspension. MeOH (3 mL) was added, and the mixture stirred at 70°C, at which point the mixture became a clear solution. The sample was cooled to RT with stirring over 30 min then stirred overnight at RT. The resulting precipitate was collected by vacuum filtration and rinsed with EtOH (0.5 mL) and dried to provide Compound 2-21·DPTTA (0.116 g, 0.145 mmol, 36%) as a white solid. Chiral purity analysis was performed using a Waters ^TM Ultra-Performance Convergence Chromatography (UPC2) ^TM supercritical fluid chromatography (SFC) system, equipped with a UV Detector (WatersTM Acquity UPC2 PDA Detector ^TM ) and mass spectrometer (Waters ^TM Acquity QDa Detector ^TM ). A Chiral Technologies Inc ^TM ChiralPak ^TM IBU/SFC 1.6 µm, 2.1 mm x 50 mm column was used with an isocratic gradient at 95% CO2 and 5% 0.5% DMEA in MeOH, at 1.5 mL/min, 40°C, and 1500 psi back pressure regulator. An extracted wavelength of 281 nm was used for %ee quantification and analysis. An optical purity of 100% ee as a single diastereomer was determined by chiral SFC analysis. The assigned structure was confirmed by a single crystal x-ray structure. Single Crystal X-Ray Structure of (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol DPTTA salt (Compound 2- 21·DPTTA). (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4, 6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol DPTTA salt (Compound 2-21·DPTTA, < 1 mg) was combined with a 50:50 EtOH/MeOH mixture (0.2 mL). The sample was heated to approximately 50°C in a capped vial to obtain a clear solution, which was then allowed to cool to RT. The solution remained clear after 2d at RT and was allowed to evaporate slowly. In 3d, the solution was found to contain blocks of single crystal quality. The crystal structure of Compound 2-21·DPTTA was determined to be a mixed ethanol and methanol solvate with formula C25H34NO4·C20H17O8·0.851(C2H6O)·0.149(CH4O). The solvate was refined as disordered between majority ethanol and minority methanol. Chiral centers at N1 (protonated), C2, C3, and C5 were all determined to have R configuration. Chiral centers at C27 and C28 (O,O′-di-p-toluoyl-tartaric acid) both have S configuration. The unit system and space group for Compound 2-21·DPTTA are shown in Table 1. Data collection and refinement parameters for Compound 2-21·DPTTA are shown in Table 2. EXAMPLE 4A: Preparation of 6-(benzyloxy)-7-methoxy-3,4-dihydroisoquinoline hydrochloride (Compound 2-16). To a solution of 6-(benzyloxy)-7-methoxy-3,4-dihydroisoquinoline (23.2 g, 86.6 mmol, 1.0 eq) in 1:1 MTBE/THF (230 mL) was added HCl (4M in dioxanes, 22.7 mL, 91.0 mmol, 1.05 eq) dropwise at rt over the course of 20 minutes. The mixture was stirred 16h at RT. The precipitate was filtered and rinsed with MTBE (100 mL) to give 6-(benzyloxy)-7-methoxy-3,4-dihydroisoquinoline hydrochloride (Compound 2-16, 25.8 g, 84.9 mmol, 98%) as a yellow solid. ¹ H NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 12.94 (br s, 1H), 8.94 (s, 1H), 7.54 (s, 1H), 7.49 - 7.46 (m, 2H), 7.45 - 7.40 (m, 2H), 7.40 - 7.35 (m, 1H), 7.29 (s, 1H), 5.27 (s, 2H), 3.88 - 3.84 (m, 2H), 3.81 (s, 3H), 3.06 (t, J = 8.4 Hz, 2H). EXAMPLE 4B: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22). To a solution of (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4, 6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 2-21, 1.950 g, 4.74 mmol, 1.0 eq) in 3:1 MeOH:H2O (20 mL) was added aq. HCl (12.1 M, 0.47 mL, 5.69 mmol, 1.2 eq) dropwise at 0°C with stirring. The mixture was stirred 10 min. Palladium on carbon (10% w/w, 0.252 g, 0.237 mmol, 0.05 eq) and ammonium formate (2.988 g, 47.4 mmol, 10 eq) were added and mixture was stirred at 50°C for 30 min. The mixture was cooled to 0°C and acidified to pH = 1 with aq. HCl (12.1 M). The suspension was filtered, and solids rinsed with MeOH (4 mL). The filtrate was transferred to a round bottom flask equipped with a stir bar and basified to pH = 7 with aq. NaOH (6 M). The volume was reduced to 20 mL by concentration in vacuo at which point white solids had precipitated. The solids were collected by vacuum filtration to provide (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinoline-2,9-dio l (Compound 2-22, 1.041 g, 3.24 mmol, 68%) as a white solid. ¹ H NMR (500 MHz, DMSO-d6): δ (ppm) 8.70 (s, 1H), 6.69 (s, 1H), 6.45 (s, 1H), 4.58 (d, J = 4.9 Hz, 1H), 3.72 (s, 3H), 3.32 - 3.25 (m, 2H), 2.98 (br d, J = 11.0 Hz, 1H), 2.90 - 2.77 (m, 3H), 2.47 - 2.42 (m, 2H), 2.32 - 2.26 (m, 1H), 2.02 (t, J = 10.4 Hz, 1H), 1.23 (q, J = 11.6 Hz, 1H), 1.17 (s, 9H). EXAMPLE 4C: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22). Step 1: Preparation of 4-(tert-butoxy)-3-oxobutanoic acid (Compound 2-15). To a suspension of ethyl 4-(tert-butoxy)-3-oxobutanoate (Compound 2-14, 100 g, 494 mmol, 1.0 eq) in water (1 L) at 0°C was added aq.6N NaOH (173 mL, 1040 mmol, 2.1 eq) over 5 minutes then the mixture was stirred for 16h at RT. The reaction mixture was acidified with aq. H ₂ SO ₄ (18.1 M) to pH 1-2 and extracted five times with MTBE. The combined organic extracts were dried with MgSO4, filtered, and concentrated in vacuo to give 4-(tert-butoxy)-3-oxobutanoic acid (Compound 2-15, 83.8 g, 481 mmol, 97%) as a clear light brown oil that was used without further purification. ¹ H NMR (500 MHz, DMSO-d ₆ ): δ (ppm) 12.53 (bs, 1H), 4.05 (s, 2H), 3.43 (s, 2H), 1.14 (s, 9H). Step 2: Preparation of 1-(tert-butoxy)propan-2-one (Compound 2-25). A solution of 4-(tert-butoxy)-3-oxobutanoic acid (Compound 2-15, 83.8 g, 481 mmol) in DMSO (166 mL) was heated with stirring at 45°C for 20h. The mixture was subjected to vacuum distillation to give 1-(tert-butoxy)propan-2-one (Compound 2-25, 55.1 g, 423 mmol, 88%) as a clear colorless oil with a boiling point of 50°C at 12 mmHg. ¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) 3.96 (s, 2H), 2.20 (s, 3H), 1.25 (s, 9H). Step 3: Preparation of 3-(tert-butoxy)-4-(dimethylamino)butan-2-one (Compound 2-26). To a solution of 1-(tert-butoxy)propan-2-one (Compound 2-25, 55.1 g, 423.3 mmol, 1.0 eq) in EtOH (275 mL) was added dimethylamine hydrochloride (51.8 g, 635 mmol, 1.5 eq), paraformaldehyde (25.4 g, 847 mmol, 2.0 eq) and aq. HCl (12.1 N, 1.75 mL, 21.2 mmol, 0.05 eq) and the mixture was stirred at 75°C for 22h. The mixture was cooled to RT, diluted with water, basified to pH = 12 with aq. NaOH (1M) and extracted five times with MTBE. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude material was split and submitted to two separate separations: a silica gel column (330 g) loaded using DCM run with an increasing gradient of MeOH (0-10% over 20 min) in DCM and a silica gel column (220 g) loaded using DCM run with an increasing gradient of MeOH (0-10% over 20 min) in DCM to give 3-(tert- butoxy)-4-(dimethylamino)butan-2-one (Compound 2-26, 25.1 g, 83% purity (w/w), 111 mmol, 26%) as an oil. ¹ H NMR (400 MHz, DMSO-d6): δ (ppm) 3.94 (t, J = 6.6 Hz, 1H), 2.45 – 2.35 (m, 2H), 2.13 (s, 6H), 2.08 (s, 3H), 1.10 (s, 9H). Step 4: Preparation of (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one (Compound (±)-2-18). To a solution of 3-(tert-butoxy)-4-(dimethylamino)butan-2-one (Compound 2-26, 25.1 g, 83% purity (w/w), 111 mmol, 1.2 eq) in MeOH (110 mL) and water (58 mL) was added 6- (benzyloxy)-7-methoxy-3,4-dihydroisoquinoline hydrochloride (Compound 2-16, 28.3 g, 93.0 mmol, 1.0 eq), sodium acetate (9.27 g, 113 mmol, 1.2 eq) and acetic acid (6.5 mL, 113 mmol, 1.2 eq). The mixture was stirred 40h at 45°C at which point a precipitate was formed. The mixture was cooled to room temperature and the precipitate was filtered. The solids were rinsed with 50% (v/v) MeOH in water (200 mL) and dried in vacuo for 16h to give (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one (Compound (±)-2-18, 20.6 g, 50.3 mmol, 54%). ¹ H NMR (400 MHz, DMSO-d ₆ ) δ (ppm): 7.46 - 7.31 (m, 5H), 6.81 (s, 1H), 6.75 (s, 1H), 5.03 (s, 2H), 4.37 (dd, J = 7.0, 10.9 Hz, 1H), 3.74 (s, 3H), 3.46 (br d, J = 11.9 Hz, 1H), 3.23 - 3.09 (m, 2H), 2.95 - 2.84 (m, 2H), 2.70 - 2.62 (m, 1H), 2.59 - 2.42 (m, 3H), 1.15 (s, 9H). Step 5: Preparation of (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-19). To a solution of 9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexah ydro-2H- pyrido[2,1-a]isoquinolin-2-one (Compound (±)-2-18, 20.6 g, 50.3 mmol, 1.0 eq) in THF (200 mL) at 0°C was added DIBAL-H (1.0 M in hexanes, 75.4 mL, 75.4 mmol, 1.5 eq) dropwise. The mixture was stirred 2h at 0°C. The mixture was warmed to RT then an additional DIBAL-H (1.0 M in hexanes, 25.1 mL, 25.1 mmol, 0.5 eq) was added dropwise. The mixture was stirred 16h at RT. The reaction mixture was cooled to 0°C then quenched with acetone. The mixture was warmed to RT, diluted with DCM (200 mL) and aq. Rochelle’s salt (10% w/w) and stirred vigorously until the emulsion dissipated. The mixture was extracted three times with MTBE. The combined organic extracts were dried over MgSO4, filtered and concentrated in vacuo to afford crude (±)-9-(benzyloxy)-3-(tert- butoxy)-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]i soquinolin-2-ol as a mixture of diastereomers (Compound (±)-2-19, 20.5 g, 49.8 mmol, 99%) that was carried on directly to the next step (synthesis of Compound 2-21). Step 6: Preparation of (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 2-21). To a solution of crude (±)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound (±)-2-19, 20.5 g, 49.8 mmol, 1.0 eq) in EtOH (440 mL) was added (2S,3S)-2,3-bis(4-methylbenzoyloxy)butanedioic acid (DPTTA, 19.2 g, 49.8 mmol, 1.0 eq). The solution was heated to reflux with stirring which became a suspension upon further heating. After the addition of MeOH (150 mL) the mixture was held at reflux until a clear solution was obtained. The solution was cooled to 75°C, then seeded with Compound 2-21·DPTTA (0.070 g, see Example 1) and held at constant temperature for 30 min. The mixture was cooled at a rate of 8°C per h to RT, then continued stirring for 16h. The resulting precipitate was collected by vacuum filtration, washed with MTBE (100 mL) and EtOH (40 mL), and dried in vacuo for 16h to provide Compound 2-21·DPTTA (16.1 g, 20.1 mmol, 40% from Compound (±)-2-18) as a white solid. An optical purity of 100% ee was determined by chiral supercritical fluid chromatography (SFC) analysis and a diastereomeric purity ≥ 99%. The chiral salt pair was suspended in DCM and water was added. The mixture was basified with saturated aq. NH ₄ OH until pH ~ 10. The mixture was extracted three times with DCM. The organic extracts were dried over MgSO4, filtered and concentrated in vacuo to afford (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 2-21, 8.13 g, 19.8 mmol, 39% from Compound (±)-2-18) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ (ppm) 7.45 - 7.41 (m, 2H), 7.41 - 7.37 (m, 2H), 7.34 - 7.31 (m, 1H), 6.77 (s, 1H), 6.74 (s, 1H), 5.01 (s, 2H), 4.61 (d, J = 4.7 Hz, 1H), 3.73 (s, 3H), 3.32 - 3.27 (m, 2H), 3.02 (br d, J = 11.0 Hz, 1H), 2.92 - 2.82 (m, 3H), 2.54 - 2.45 (m, 2H), 2.35 - 2.29 (m, 1H), 2.04 (br t, J = 10.3 Hz, 1H), 1.27 - 1.21 (m, 1H), 1.17 (s, 9H). Step 6: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22). To a solution of (2R,3R,11bR)-9-(benzyloxy)-3-(tert-butoxy)-10-methoxy-1,3,4, 6,7,11b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 2-21, 8.13 g, 19.8 mmol, 1.0 eq) in 3:1 MeOH:H2O (42 mL) was added aq. HCl (12.1 M, 1.97 mL, 23.8 mmol, 1.2 eq) dropwise at 0°C with stirring. The mixture was stirred 10 min. Palladium on carbon (10% w/w, 1.06 g, 0.994 mmol, 0.05 eq) and ammonium formate (12.5 g, 198 mmol, 10 eq) were added and mixture was stirred at 50°C for 30 min. The mixture was cooled to 0°C and acidified to pH = 1 with aq. HCl (12.1 M). The suspension was filtered, and solids rinsed with MeOH. The filtrate was transferred to a round bottom flask equipped with a stir bar and basified to pH = 8 with aq. NaOH (6 M) at which point white solids had precipitated. The solids were collected by vacuum filtration and dried in vacuo 16h to provide (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1-a]isoquinoline- 2,9-diol (Compound 2-22, 5.74 g, 17.9 mmol, 90%) as a white solid. ¹ H NMR (500 MHz, DMSO- d6): δ (ppm) 8.70 (s, 1H), 6.69 (s, 1H), 6.45 (s, 1H), 4.58 (d, J = 4.9 Hz, 1H), 3.72 (s, 3H), 3.32 - 3.25 (m, 2H), 2.98 (br d, J = 11.0 Hz, 1H), 2.90 - 2.77 (m, 3H), 2.47 - 2.42 (m, 2H), 2.32 - 2.26 (m, 1H), 2.02 (t, J = 10.4 Hz, 1H), 1.23 (q, J = 11.6 Hz, 1H), 1.17 (s, 9H). EXAMPLE 5: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(2,2,2- trifluoroethoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]iso quinolin-2-ol (Compound 17). To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 0.060 g, 0.187 mmol, 1.0 eq) in DMF (1.8 mL) was added cesium carbonate (0.183 g, 0.561 mmol, 3.0 eq) and the resulting mixture stirred at RT for 10 min. Then, 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.056 g, 0.243 mmol, 1.3 eq) was added and the mixture was stirred for 3h. The mixture was diluted with EtOAc and rinsed five times with water. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was submitted to three chromatographic separations: a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-60% over 20 min) in hexanes, a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-70% over 25 min), and a reversed-phase C ₁₈ column (6 g) loaded using DMSO run with an increasing gradient of ACN (10- 50% over 20 min) in water to afford (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(2,2,2- trifluoroethoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]iso quinolin-2-ol (Compound 17, 0.042 g, 0.104 mmol, 56%) as a white solid. Obs. Ion (m/z) = 404.3 [M+H] ⁺ . ¹ H NMR (500 MHz, DMSO-d ₆ ): δ (ppm) 6.83 (s, 1H), 6.78 (s, 1H), 4.66 - 4.58 (m, 3H), 3.76 (s, 3H), 3.38 - 3.26 (m, 2H), 3.04 (br d, J = 11.0 Hz, 1H), 2.93 - 2.81 (m, 3H), 2.57 - 2.46 (m, 2H), 2.35 - 2.29 (m, 1H), 2.08 - 2.02 (m, 1H), 1.29 - 1.20 (m, 1H), 1.17 (s, 9H). EXAMPLE 6: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(3,3,3- trifluoropropoxy)-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]is oquinolin-2-ol (Compound 18). Batch A To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, see Example 4B, 0.150 g, 0.467 mmol, 1.0 eq) in MeOH (1.5 mL) was added cesium carbonate (0.456 g, 1.40 mmol, 3.0 eq) and the resulting mixture stirred at RT for 10 min. Then, 3,3,3-trifluoropropyl trifluoromethanesulfonate (0.149 g, 0.607 mmol, 1.3 eq) was added and the mixture was stirred at RT for 2h, then a second portion was added (0.230 g, 0.934 mmol, 2.0 eq) and the mixture was stirred an additional 1h. The mixture was diluted with water and extracted three times with DCM. The combined organic extracts were dried over MgSO ₄ , filtered, and concentrated in vacuo. The crude material was submitted to two chromatographic separations: a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-80% over 20 min) in hexanes and a reversed-phase C ₁₈ column (16 g) loaded using DMSO run with an increasing gradient of ACN (10-40% over 20 min) in water to afford (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(3,3,3-trifluoropr opoxy)-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 18, 0.147 g, 0.352 mmol, 75%) as a white solid. Obs. Ion (m/z) = 418.3 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d6): δ (ppm) 6.77 (s, 1H), 6.69 (s, 1H), 4.58 (d, J = 4.8 Hz, 1H), 4.12 (t, J = 6.1 Hz, 2H), 3.72 (s, 3H), 3.36 - 3.24 (m, 2H), 3.02 (br d, J = 10.9 Hz, 1H), 2.93 - 2.81 (m, 3H), 2.81 - 2.69 (m, 2H), 2.59 - 2.42 (m, 2H), 2.36 - 2.27 (m, 1H), 2.09 - 2.00 (m, 1H), 1.24 (q, J = 14.5 Hz, 1H), 1.17 (s, 9H). Batch B To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, see Example 4C, 0.450 g, 1.40 mmol, 1.0 eq) in MeOH (4.5 mL) was added cesium carbonate (1.37 g, 4.20 mmol, 3.0 eq) and the resulting mixture stirred at RT for 10 min. Then, 3,3,3-trifluoropropyl trifluoromethanesulfonate (0.689 g, 2.80 mmol, 2.0 eq) was added and the mixture was stirred at RT for 16h, then a second portion was added (0.689 g, 2.80 mmol, 2.0 eq) and the mixture was stirred an additional 3h. The mixture was diluted with water and extracted three times with DCM. The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude material was submitted to two chromatographic separations: a silica gel column (12 g) loaded using DCM run with an increasing gradient of EtOAc (0-60% over 20 min) in hexanes and a reversed-phase C18 column (16 g) loaded using DMSO run with an increasing gradient of ACN (10-40% over 20 min) in water to afford (2R,3R,11bR)-3-(tert- butoxy)-10-methoxy-9-(3,3,3-trifluoropropoxy)-1,3,4,6,7,11b- hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 18, 0.446 g, 1.07 mmol, 76%) as a white solid. ¹ H NMR (400 MHz, DMSO-d6): δ (ppm) 6.77 (s, 1H), 6.69 (s, 1H), 4.58 (d, J = 4.8 Hz, 1H), 4.12 (t, J = 6.1 Hz, 2H), 3.72 (s, 3H), 3.36 - 3.24 (m, 2H), 3.02 (br d, J = 10.9 Hz, 1H), 2.93 - 2.81 (m, 3H), 2.81 - 2.69 (m, 2H), 2.59 - 2.42 (m, 2H), 2.36 - 2.27 (m, 1H), 2.09 - 2.00 (m, 1H), 1.24 (q, J = 14.5 Hz, 1H), 1.17 (s, 9H). EXAMPLE 7: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9-cyclopropoxy-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 19). To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 0.120 g, 0.373 mmol, 1.0 eq) in DMF (4 mL) was added cesium carbonate (0.365 g, 1.12 mmol, 3.0 eq) and the resulting mixture stirred at RT for 10 min. Then, cyclopropyl trifluoromethanesulfonate (0.106 g, 0.559 mmol, 1.5 eq) was added and the mixture was stirred overnight. An additional portion of cyclopropyl trifluoromethanesulfonate (0.071 g, 0.373 mmol, 1.0 eq) was added and the mixture was stirred 2h at 50°C. The mixture was cooled to RT, diluted with EtOAc, and rinsed five times with water. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. A silica gel column (4 g) was loaded using DCM and run with an increasing gradient of EtOAc (0-100% over 25 min) in hexanes to afford crude (2R,3R,11bR)- 3-(tert-butoxy)-9-cyclopropoxy-10-methoxy-1,3,4,6,7,11b-hexa hydro-2H-pyrido[2,1-a]isoquinolin-2- ol (Compound 19, 0.130 g, 0.360 mmol) as an off white solid. To remove trace impurities, crude Compound 19 (0.130 g, 0.360 mmol, 1.0 eq) was dissolved in anhydrous THF (2.8 mL) under an atmosphere of nitrogen at 0°C with stirring. A solution of lithium aluminum hydride in THF (2 M, 0.40 mL, 0.810 mmol, 2.25 eq) was added dropwise over 10 min. The temperature was increased to 60°C and stirred for 3h. An additional portion of lithium aluminum hydride in THF (2 M, 0.18 mL, 0.360 mmol, 1.0 eq) was added and the mixture was stirred overnight at 60°C. The mixture was cooled to 0°C then sodium sulfate decahydrate (0.116 g, 0.360 mmol, 1.0 eq) was added over the course of 10 min then allowed to stir 20 min. The mixture was filtered over celite, the filter cake was rinsed with EtOAc, and the solvent was removed in vacuo. The crude material was chromatographed using a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-100% over 25 min) in hexanes to afford (2R,3R,11bR)-3-(tert-butoxy)-9-cyclopropoxy-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 19, 0.074 g, 0.205 mmol, 57%) as a white solid. Obs. Ion (m/z) = 362.3 [M+H] ⁺ . ¹ H NMR (500 MHz, DMSO-d ₆ ): δ (ppm) 6.89 (s, 1H), 6.73 (s, 1H), 4.60 (d, J = 4.9 Hz, 1H), 3.75 (tt, J = 2.9, 6.0 Hz, 1H), 3.69 (s, 3H), 3.31 - 3.25 (m, 2H), 3.02 (br d, J = 11.5 Hz, 1H), 2.96 - 2.82 (m, 3H), 2.58 - 2.43 (m, 2H), 2.38 - 2.28 (m, 1H), 2.08 - 2.01 (m, 1H), 1.30 - 1.20 (m, 1H), 1.17 (s, 9H), 0.75 - 0.70 (m, 2H), 0.64 - 0.59 (m, 2H). EXAMPLE 8: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9-ethoxy-10-methoxy-1,3,4,6,7,1 1b- hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 22). To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 0.150 g, 0.467 mmol, 1.0 eq) in DMF (1.5 mL) was added cesium carbonate (0.456 g, 1.40 mmol, 3.0 eq) and the resulting mixture stirred at RT for 10 min. Then, ethyl iodide (0.058 g, 0.375 mmol, 0.8 eq) was added and the mixture was stirred at RT for 1h. The mixture was diluted with EtOAc (100 mL) and rinsed five times with water (5 mL). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was submitted to two chromatographic separations: a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-100% over 20 min) in hexanes and a reversed-phase C18 column (16 g) loaded using DMSO run with an increasing gradient of ACN (10-30% over 15 min) in water to afford (2R,3R,11bR)-3-(tert-butoxy)-9-ethoxy-10-methoxy-1,3,4,6,7,1 1b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 22, 0.123 g, 0.352 mmol, 75%) as a white solid. Obs. Ion (m/z) = 350.3 [M+H] ⁺ . ¹ H NMR (500 MHz, DMSO-d6): δ (ppm) 6.73 (s, 1H), 6.61 (s, 1H), 4.60 (d, J = 4.7 Hz, 1H), 3.97 - 3.91 (m, 2H), 3.71 (s, 3H), 3.31 - 3.25 (m, 1H), 3.01 (br d, J = 10.7 Hz, 1H), 2.92 - 2.81 (m, 3H), 2.54 - 2.44 (m, 2H), 2.35 - 2.28 (m, 1H), 2.07 - 2.01 (m, 1H), 1.29 (t, J = 6.8 Hz, 3H), 1.23 - 1.23 (m, 1H), 1.24 (q, J = 11.7 Hz, 1H), 1.17 (s, 9H). EXAMPLE 9: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopropylmethoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 25). To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 0.150 g, 0.467 mmol, 1.0 eq) in DMF (1.5 mL) was added cesium carbonate (0.456 g, 1.40 mmol, 3.0 eq) and the resulting mixture was stirred at RT for 10 min. Then, (bromomethyl)cyclopropane (0.069 g, 0.514 mmol, 1.1 eq) was added and the mixture stirred at RT overnight. The mixture was diluted with EtOAc (100 mL) and rinsed five times with water (5 mL). The organic layer was dried over MgSO ₄ , filtered, and concentrated in vacuo. A silica gel column (12 g) was loaded using DCM and run with an increasing gradient of EtOAc (0- 100% over 20 min) in hexanes to afford (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopropylmethoxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 25, 0.107 g, 0.285 mmol, 61%) as a white solid. Obs. Ion (m/z) = 376.3 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 6.73 (s, 1H), 6.59 (s, 1H), 4.57 (d, J = 4.8 Hz, 1H), 3.76 - 3.68 (m, 2H), 3.72 (s, 3H), 3.35 - 3.24 (m, 2H), 3.01 (br d, J = 11.1 Hz, 1H), 2.94 - 2.78 (m, 3H), 2.55 - 2.43 (m, 2H), 2.38 - 2.24 (m, 1H), 2.04 (br t, J = 10.3 Hz, 1H), 1.28 - 1.18 (m, 1H), 1.17 (s, 9H), 0.58 - 0.49 (m, 2H), 0.33 - 0.23 (m, 2H). EXAMPLE 10: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9-((3,3- difluorocyclobutyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 38). To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 0.150 g, 0.467 mmol, 1.0 eq) in DMF (4.5 mL) was added cesium carbonate (0.456 g, 1.40 mmol, 3.0 eq) and the resulting mixture stirred at RT for 10 min. Then, 3-(bromomethyl)-1,1-difluorocyclobutane (0.173 g, 0.934 mmol, 2 eq) was added and the mixture stirred at 50°C for 3 h. The mixture was diluted with EtOAc and rinsed five times with water. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was submitted to three chromatographic separations: a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-70% over 20 min) in hexanes and two reversed- phase C18 column (6 g) loaded using DMSO run with an increasing gradient of MeCN (10-50% over 20 min) in water to afford (2R,3R,11bR)-3-(tert-butoxy)-9-((3,3-difluorocyclobutyl)meth oxy)-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 38, 0.120 g, 0.282 mmol, 60%) as a white solid. Obs. Ion (m/z) = 426.3 [M+H] ⁺ . ¹ H NMR (500 MHz, DMSO-d ₆ ): δ (ppm) 6.76 (s, 1H), 6.67 (s, 1H), 4.59 (d, J = 4.5 Hz, 1H), 3.96 (br d, J = 6.2 Hz, 2H), 3.73 (s, 3H), 3.36 - 3.25 (m, 4H), 3.02 (br d, J = 11.1 Hz, 1H), 2.94 - 2.81 (m, 3H), 2.76 - 2.63 (m, 2H), 2.60 - 2.28 (m, 4H), 2.05 (br t, J = 10.3 Hz, 1H), 1.30 - 1.20 (m, 1H), 1.18 (s, 9H). EXAMPLE 11: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9-(((S)-2,2- difluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 43). To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 0.088 g, 0.274 mmol, 1.0 eq) in DMF (2.5 mL) was added cesium carbonate (0.268 g, 0.822 mmol, 3.0 eq) and the resulting mixture stirred at RT for 10 min. Then, (2R)-2-(bromomethyl)-1,1-difluorocyclopropane (0.070 g, 0.411 mmol, 1.5 eq) was added and the mixture was stirred at RT overnight. The mixture was diluted with EtOAc and rinsed five times with water. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was submitted to two chromatographic separations: a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-70% over 12 min) in hexanes and a reversed-phase C ₁₈ column (6 g) loaded using DMSO run with an increasing gradient of ACN (10- 70% over 20 min) in water to afford (2R,3R,11bR)-3-(tert-butoxy)-9-(((S)-2,2- difluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1-a]isoquinolin-2- ol (Compound 43, 0.023 g, 0.056 mmol, 20%) as a white solid. Obs. Ion (m/z) = 412.3 [M+H] ⁺ . ¹ H NMR (500 MHz, DMSO-d ₆ ): δ (ppm) 6.76 (s, 1H), 6.65 (s, 1H), 4.61 (d, J = 4.7 Hz, 1H), 4.04 (ddd, J = 3.1, 6.8, 10.3 Hz, 1H), 3.90 (t, J = 9.6 Hz, 1H), 3.73 (s, 3H), 3.38 – 3.28 (m, 2H), 3.02 (br d, J = 11.0 Hz, 1H), 2.93 - 2.81 (m, 3H), 2.54 – 2.46 (m, 2H), 2.35 - 2.28 (m, 1H), 2.25 - 2.13 (m, 1H), 2.04 (br t, J = 10.4 Hz, 1H), 1.70 (ddt, J = 4.8, 7.8, 12.0 Hz, 1H), 1.46 - 1.38 (m, 1H), 1.24 (q, J = 11.5 Hz, 1H), 1.17 (s, 9H). EXAMPLE 12: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9-(((R)-2,2- difluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 44). Method A To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 0.130 g, 0.404 mmol, 1.0 eq) in DMF (4.0 mL) was added cesium carbonate (0.394 g, 1.21 mmol, 3.0 eq) and the resulting mixture stirred at RT for 10 min. Then, (2S)-2-(bromomethyl)-1,1-difluorocyclopropane (0.104 g, 0.606 mmol, 1.5 eq) was added and the mixture was stirred at RT overnight. The mixture was diluted with EtOAc and rinsed five times with water. The organic layer was dried over MgSO ₄ , filtered, and concentrated in vacuo. The crude material was submitted to two chromatographic separations: a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-70% over 15 min) in hexanes and a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-70% over 20 min) in hexanes to afford (2R,3R,11bR)-3-(tert-butoxy)-9-(((R)-2,2-difluorocyclopropyl )methoxy)- 10-methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinol in-2-ol (Compound 44, 0.131 g, 0.318 mmol, 79%) as a white solid. Obs. Ion (m/z) = 412.3 [M+H] ⁺ . ¹ H NMR (500 MHz, DMSO-d6): δ (ppm) 6.76 (s, 1H), 6.65 (s, 1H), 4.60 (d, J = 4.9 Hz, 1H), 4.09 - 4.03 (m, 1H), 3.89 (t, J = 9.7 Hz, 1H), 3.73 (s, 3H), 3.36 – 3.26 (m, 2H), 3.01 (br d, J = 11.2 Hz, 1H), 2.93 - 2.80 (m, 3H), 2.56 - 2.44 (m, 2H), 2.35 - 2.28 (m, 1H), 2.24 - 2.13 (m, 1H), 2.07 - 2.01 (m, 1H), 1.69 (ddt, J = 4.7, 7.8, 12.0 Hz, 1H), 1.46 - 1.38 (m, 1H), 1.30 - 1.20 (m, 1H), 1.17 (s, 9H). Method B To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 0.200 g, 0.622 mmol, 1.0 eq) in degassed toluene (4.0 mL) was added (R)-(2,2-difluorocyclopropyl)methanol (0.134 g, 1.24 mmol, 2.0 eq) and (tributylphosphoranylidene)acetonitrile (0.299 g, 1.24 mmol, 2.0 eq) in a capped microwave vial. The headspace was evacuated and backfilled with nitrogen three times. The resulting mixture was stirred at 100°C under microwave irradiation for 2 h. The mixture was passed through a celite filter and concentrated in vacuo. The crude material was submitted to three chromatographic separations: a silica gel column (4 g) loaded using DCM run with an increasing gradient of EtOAc (0-70% over 15 min) in hexanes and two reversed-phase C18 column (6 g) loaded using DMSO run with an increasing gradient of MeCN (10-50% over 20 min) to afford (2R,3R,11bR)-3-(tert-butoxy)-9-(((R)- 2,2-difluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-he xahydro-2H-pyrido[2,1- a]isoquinolin-2-ol (Compound 44, 0.108 g, 0.262 mmol, 42%) as a white solid. Obs. Ion (m/z) = 412.3 [M+H] ⁺ . ¹ H NMR (500 MHz, DMSO-d6): δ (ppm) 6.76 (s, 1H), 6.65 (s, 1H), 4.60 (d, J = 4.9 Hz, 1H), 4.09 - 4.03 (m, 1H), 3.89 (t, J = 9.7 Hz, 1H), 3.73 (s, 3H), 3.36 – 3.26 (m, 2H), 3.01 (br d, J = 11.2 Hz, 1H), 2.93 - 2.80 (m, 3H), 2.56 - 2.44 (m, 2H), 2.35 - 2.28 (m, 1H), 2.24 - 2.13 (m, 1H), 2.07 - 2.01 (m, 1H), 1.69 (ddt, J = 4.7, 7.8, 12.0 Hz, 1H), 1.46 - 1.38 (m, 1H), 1.30 - 1.20 (m, 1H), 1.17 (s, 9H). EXAMPLE 12A: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9-isopropoxy-10-methoxy- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol (Compound 23). To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 0.300 g, 0.933 mmol, 1.0 eq) in DMF (10 mL) was added cesium carbonate (0.912 g, 2.80 mmol, 3.0 eq) and the resulting mixture stirred at RT for 10 min. Then, 2-iodopropane (0.206 g, 1.21 mmol, 1.3 eq) was added and the mixture was stirred at RT overnight. The mixture was concentrated in vacuo, then diluted with EtOAc and rinsed two times with water. The aqueous wash was extracted two times with EtOAc. The combined organic extracts were rinsed two times with 10% LiCl aqueous solution. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was submitted to two chromatographic separations: a silica gel column (12 g) dry loaded using celite with an increasing gradient of EtOAc (0-55% over 15 min) in hexanes and a reversed-phase C18 column (16 g) loaded using DMSO run with an increasing gradient of ACN (0-55% over 20 min) in water to afford (2R,3R,11bR)-3-(tert- butoxy)-9-isopropoxy-10-methoxy-1,3,4,6,7,11b-hexahydro-2H-p yrido[2,1-a]isoquinolin-2-ol (Compound 23, 0.188 g, 0.517 mmol, 55%) as a white solid. Obs. Ion (m/z) = 364.3 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d ₆ ): δ (ppm) 6.73 (s, 1H), 6.62 (s, 1H), 4.58 (d, J = 4.8 Hz, 1H), 4.45 (spt, J = 6.1 Hz, 1H), 3.70 (s, 3H), 3.31 - 3.25(m, 2H), 3.01 (br d, J = 11.0 Hz, 1H), 2.93 - 2.80 (m, 3H), 2.56 - 2.43 (m, 2H), 2.35 - 2.27 (m, 1H), 2.08 - 2.00 (m, 1H), 1.29 - 1.23 (m, 1H), 1.22 (dd, J = 6.0, 1.8 Hz, 6H), 1.17 (s, 9H). EXAMPLE 12B: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopropylmethoxy-d ₂ )-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 99). Step 1: Preparation of (iodomethyl-d2)cyclopropane. To a solution of triphenylphosphine (7.40 g, 28.2 mmol, 1.2 eq) in DCM (100 mL) was added I2 (6.57 g, 25.9 mmol, 1.1 eq) at RT. The reaction mixture was stirred at RT for 30 min. Imidazole (2.40 g, 35.3 mmol, 1.5 eq) and cyclopropylmethan-d2-ol (1.74 g, 23.5 mmol, 1.0 eq) were sequentially added at RT. The reaction mixture was stirred at RT for 16 h. The mixture was quenched with saturated aq. Na ₂ S ₂ O ₃ . The aqueous layer was extracted three times with diethyl ether. The combined organic extracts were dried over Na ₂ SO ₄ , filtered, and concentrated under reduced pressure. A silica gel column (24 g) was loaded using hexanes and run with pentane to afford (iodomethyl- d ₂ )cyclopropane (2.30 g, 12.5 mmol, 53% yield) as a colorless oil. ¹ H NMR (400 MHz, benzene-d ₆ ): δ (ppm) 0.87 (ddtdd, J = 9.1, 5.7, 4.7, 2.4, 1.0 Hz, 1H), 0.42 - 0.33 (m, 2H), −0.11 - −0.18 ppm (m, 2H). Step 2: Preparation of (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopropylmethoxy-d ₂ )-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol (Compound 99). To a solution of (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H- pyrido[2,1-a]isoquinoline-2,9-diol (Compound 2-22, 2.00 g, 6.22 mmol, 1.0 eq) in DMF (60 mL) was added cesium carbonate (5.05 g, 15.5 mmol, 2.5 eq) and the resulting mixture was stirred at 0 °C for 30 min. Then, (iodomethyl-d2)cyclopropane (1.20 g, 6.53 mmol, 1.05 eq) was added and the mixture stirred at 0 °C overnight. The mixture was diluted with water (200 mL) and extracted with DCM (5×100 mL). The combined organic layer was dried over Na ₂ SO ₄ , filtered, and concentrated in vacuo. The residue was purified by with a silica gel column (24 g) that was loaded using DCM and run with an increasing gradient of EtOAc (0-100% over 20 min) in hexanes, followed by a C18 reverse phase column (150 g) loaded using DMSO and run with an increasing gradient of MeCN (5- 60% over 20 min) in H ₂ O, followed by recrystallization in hexanes/ethyl acetate to afford (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopropylmethoxy-d ₂ )-10-methoxy-1,3,4,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol (Compound 99, 1.80 g, 4.76 mmol, 77% yield, 97.6% as d ₂ , 1.2% as d ₁ , and 1.2% non-deuterated, each as determined by MS (QTOF)) as a white solid. Obs. Ion (m/z) = 378.4 [M+H] ⁺ . ¹ H NMR (400 MHz, DMSO-d): δ (ppm) 6.73 (s, 1H), 6.58 (s, 1H), 4.57 (d, J = 4.8 Hz, 1H), 3.72 (s, 3H), 3.31 - 3.22 (m, 2H), 3.01 (br d, J = 11.0 Hz, 1H), 2.94 - 2.78 (m, 3H), 2.56 - 2.51 (m, 1H), 2.46 (br d, J = 9.0 Hz, 1H), 2.36 - 2.25 (m, 1H), 2.04 (br t, J = 10.4 Hz, 1H), 1.30 - 1.20 (m, 1H), 1.20 – 1.06 (m, 10H), 0.58 - 0.49 (m, 2H), 0.31 - 0.23 ppm (m, 2H). EXAMPLE 13: Reagents used in the preparation of certain compounds described in Table A. Additional compounds shown in Table A were prepared using similar methods as described in the above examples and the following reagents shown in Table 3. Table 3 also provides the observed (Obs) ion m/z ratio for the title compound. Table 3

EXAMPLE 14: Methods for Determining VMAT2 Inhibitory Activity of a Compound. Examples of techniques for determining the capability of a compound to inhibit VMAT2 are provided below. The procedure was adapted from that described previously (see, e.g., Near, (1986), Mol. Pharmacol.30: 252-57; Teng, et al., J. Neurochem.71, 258-65, 1998). Homogenates from human platelets were prepared by homogenization and then washed by centrifugation as described previously (see, e.g., Hoare et al., (2003) Peptides 24:1881-97). The human VMAT2 K _i values for the compounds listed in Table A were determined using the following procedures. Compound dilution series in DMSO were generated from either powder stocks by hand or direct dilution using an Echo 655 (Beckman). In a total volume of 0.145mL in low- binding 96-well plates (Corning #3605), twelve concentrations of test compound were competed against 10 nM ³ H-dihydrotetrabenezine (American Radiolabeled Chemicals) on human platelet homogenate (30 µg membrane protein per well) in VMAT2 binding buffer (Dulbecco’s phosphate buffered saline, 1 mM EDTA, pH 7.4). Following incubation at 25°C for 90 minutes, bound radioligand was collected by rapid filtration onto GF/C glass fiber filters, pretreated with 0.1% polyethylenimine, using a Microlab Star (Hamilton). Following harvesting the filter plates were washed with 0.8 mL VMAT2 binding buffer, and bound radioligand was quantified by scintillation counting using a Microplate Counter Microbeta (PerkinElmer). Data from 12-point concentration response curves were analyzed to calculate an IC50 using a four-parameter logistic regression algorithm, where top was constrained to 100 and bottom was constrained to 0. The Ki value for each compound was calculated using the Cheng-Prusoff equation, utilizing a Kd of 4.06 nM for ³ H- dihydrotetrabenezine. Compound Ki (nM) values are provided in Table 4. Table 4 NT = Not Tested 1 Assayed as a mixture of trans isomers (cyclopropyl). 2 Assayed as a mixture of cis isomers (cyclopropyl). EXAMPLE 15: VMAT2 Inhibitor-Induced Reduction of Open-Field Hypolocomotor Activity. The effect of VMAT2 inhibitors on dopamine depletion was measured using the locomotor activity (LMA) assay. Following a pre-treatment time of 60 or 120 minutes, male Sprague-Dawley rats (250-350 g) were placed in a locomotor activity chamber surrounded by Infrared PhotoBeams (Med Associates). Rat locomotor activity was detected by automated counting of successive beam breaks and activity is defined as the number of beam breaks in 60 min. Data was analyzed by one-way analysis of variance (ANOVA; GraphPad Prism) followed by Dunnett’s post-hoc test for significance. The ED ₅₀ was calculated for (2R,3R,11bR)-3-(tert-butoxy)-10-methoxy-9-(3,3,3-trifluoropr opoxy)- 1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-ol Compound 18 (0.036 mg/kg, see FIG.5) and (2R,3R,11bR)-3-(tert-butoxy)-9-ethoxy-10-methoxy-1,3,4,6,7,1 1b-hexahydro-2H-pyrido[2,1- a]isoquinolin-2-ol Compound 22 (0.013 mg/kg, see FIG.5). In a similar manner as described in this example, the ED50 was calculated for the following compounds: (2R,3R,11bR)-3-(tert-butoxy)-9-cyclopropoxy-10-methoxy-1,3,4 ,6,7,11b-hexahydro-2H- pyrido[2,1-a]isoquinolin-2-ol Compound 19 (0.04 mg/kg); (2R,3R,11bR)-3-(tert-butoxy)-9-((3,3- difluorocyclobutyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahyd ro-2H-pyrido[2,1-a]isoquinolin-2-ol Compound 38 (0.06 mg/kg); (2R,3R,11bR)-3-(tert-butoxy)-9-(((S)-2,2- difluorocyclopropyl)methoxy)-10-methoxy-1,3,4,6,7,11b-hexahy dro-2H-pyrido[2,1-a]isoquinolin-2- ol Compound 43 (0.03 mg/kg); and (2R,3R,11bR)-3-(tert-butoxy)-9-(cyclopropylmethoxy-d ₂ )-10- methoxy-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin- 2-ol Compound 99 (0.03 mg/kg). EXAMPLE 16: Conditioned Avoidance Response Assay of Antipsychotic Activity. The conditioned avoidance response (CAR) test has been shown to be an effective and reliable preclinical model for assessing the antipsychotic activity of compounds. In the CAR paradigm, a rat is trained in a two-chamber shuttle box to respond to a conditioned stimulus (auditory) by negative reinforcement. If the animal fails to move to the other chamber upon presentation of an auditory stimulus, a mild foot shock is applied to the side where the rat is located. The rat learns to avoid the mild foot shock by moving to the other chamber upon initiation of the auditory signal, termed a conditioned avoidance response. Crossing to the other chamber during administration of the shock is termed an escape response. If a rat fails to move to the other chamber even upon administration of the foot shock, the rat is considered to have an escape failure. Numerous studies have shown that typical and atypical antipsychotic drugs selectively suppress CAR, thus making it an ideal assay to screen potential antipsychotic compounds (see, e.g., Wadenberg et al., Biobehav. Rev. (1999) 23: 851-62). Male Wistar rats are trained every day for 3 to 4 weeks. In the training session, rats are placed in the CAR two-way shuttle box and the training period of 20 trials ensued. A trial consisted of a 10- sec presentation of an 80 dB white noise followed by a scrambled 0.6 mA foot shock lasting up to 20 sec. The inter-trial interval ranged from 20-60 sec. The rat learns to avoid shock by moving from one compartment to the other when the conditioned stimulus is presented (a conditioned avoidance response). A rat is deemed sufficiently trained if it avoided the shock when presented with the conditioned stimulus at least 19 times out of the 20 trials. Rats that do not pass these criteria are not used. On test day, trained animals are acclimated in the test room for 30 minutes prior to testing. They are then dosed with compound and are placed in the CAR two-way shuttle box. In the test, 20 trials are performed on each rat. In each trial the conditioned stimulus is applied (10-sec presentation of 80 dB white noise), followed by the foot shock (a scrambled 0.6 mA foot shock lasting up to 20 sec). If the animal moves to the other chamber on presentation of the conditioned stimulus, it is scored as a conditioned avoidance response. If it moved upon presentation of the foot shock, it is scored as an escape. If it fails to move upon presentation of the foot shock, it is scored as an escape failure. Antipsychotic efficacy is evident by an increase in the number of escapes. Data are analyzed by analysis of variance (ANOVA) followed by post-hoc comparisons with the Bonferroni Test when appropriate. An effect is considered significant if p < 0.05. Outliers defined as two standard deviations above or below the mean are detected and are removed from all analysis. EXAMPLE 17: Method to Determine Stability of Compounds in Human Liver Microsomes. A test compound (0.5 µM) was incubated with pooled mixed gender liver microsomes from humans (0.5mg/mL total protein) at 37°C in the presence of an NADPH-generating system containing 50 mM, pH 7.4 potassium phosphate buffer, 3 mM magnesium chloride, 1 mM EDTA, 1 mM NADP, 5 mM glusose-6-phosphate, and 1 Unit/mL glucose-6-phosphate dehydrogenase. All concentrations were relative to the final incubation volume of 125 µL. Incubations were conducted at 37°C for 0, 5, 10, 20, 40, and 60 minutes in a water bath and terminated by rapid mixing with 150 µL of ice-cold acetonitrile containing internal standard. Precipitated proteins were removed by centrifugation prior to LC-MS/MS analysis. Aliquots of the resulting supernatant fractions were analyzed by LC-MS/MS monitoring for depletion of parent compound. The resultant peak area ratio versus time data was fitted to a non-linear regression using XLfit Scientific Curve Fitting Software (IDBS Ltd., Surrey, UK) and the elimination half-life (t1/2, min) was calculated from the slope. Pharmacokinetic parameters were predicted using the method described by Obach et al. (J. Pharmcol. Exp. Ther.1997; 283: 46.58). Briefly, the values for intrinsic clearance were calculated from the elimination half-life data and were then scaled to represent the clearance expected in the entire animal, see Table 5 (human). Additional values calculated included predicted extraction ratio and predicted maximum bioavailability. For very stable compounds the in vitro half-life calculated from the HLM method is maxed at 420 minutes. Accordingly, for these stable compounds the in vitro half-life is at least 420 minutes but could be greater. Further, for these stable compounds the predicted systemic clearance and scaled intrinsic clearance is at least 2.59 and 2.97 respectively but could be lower, and the predicted maximum bioavailability (%F) is at least 87 but could be higher. Table 5 (Human LM) 1 Assayed as a mixture of trans isomers (cyclopropyl). 2 Assayed as a mixture of cis isomers (cyclopropyl). EXAMPLE 18: Method to determine cytochrome P4502D63A4 (CYP3A4) and (CYP2D6) inhibition in expressed human enzymes using fluorescent marker substrates. A test compound was incubated with individually expressed human recombinant CYP enzymes systems in the presence of NADPH and IC ₅₀ values for inhibition were determined using a marker substrate approach. For CYP3A4, the test compound was incubated with expressed human CYP3A4 (Gentest Supersomes (Corning, Woburn, MA)) and IC ₅₀ values for inhibition were determined using marker substrate 7-benzyloxy-4-(trifluoromethyl)-coumarin (BFC), which is dealkylated by CYP3A4 to form the fluorescent product, 7-hydroxy-4-(trifluoromethyl)-coumarin (7-HFC). The amount of 7-HFC formed during the incubation was detected with a 96-well fluorescent plate reader (BioTek Synergy LX, Agilent, Santa Clara, CA), excitation λ 400 nm and emission λ 528 nm. For CYP2D6, the test compound was incubated with expressed human CYP2D6 (Gentest Supersomes, (Corning, Woburn, MA)) and IC ₅₀ values for inhibition were determined using marker substrate, 3-[2-(N,N-diethyl-N-methylamino) ethyl]-7-methoxy-4-methylcoumarin (AMMC), which is O-demethylated by CYP2D6 to form the fluorescent product, 3-[2-(N,N-diethyl-N- methylammonium)ethyl]-7-hydroxy-4-methylcoumarin (AHMC). The amount of AHMC formed during the incubation was monitored with a 96-well fluorescent plate reader (BioTek Synergy LX, Agilent, Santa Clara, CA), excitation λ 360 nm and emission λ 460 nm. For each enzyme assay, four concentrations of the test compound (ranging from 0.048 to 6 µM) were assessed at a single concentration of the substrate (Km), 50 µM for BFC and 1.5 µM for AMMC, respectively, in duplicate. Reactions (total volume 200µL) included 100 µL of NADPH- generating system containing 75 mM, pH 7.4 potassium phosphate buffer, 3 mM magnesium chloride, 1 mM NADP, 5 mM glusose-6-phosphate, and 1 unit/mL glucose-6-phosphate and were initiated with 100 µL of CYP enzyme solution (10 pmol), which was added immediately before the samples were incubated at 37°C. Incubations are stopped after 30 minutes by adding 75µL stop solution (80% acetonitrile / 20% 0.5M Tris Base). Ketoconazole and quinidine were used for positive controls of CYP3A4 and CYP2D6, respectively. For each CYP, the extent of inhibition, expressed as a percentage, was calculated then data were plotted on a semi-log plot [log (inhibitor) on the x-axis and percentage of control activity on the y-axis], and fitted with the following Levenberg-Marquardt algorithm: Where “A” is the bottom plateau of the curve and usually is equal to 0, “B” is the top plateau of the curve and has a typical value of 100, “C” represents “X” value at the middle of the curve, which represents the concentration of the inhibitor that causes 50% inhibition, “D” is the slope factor. The IC50 value was calculated using XLfit Scientific Curve Fitting Software (IDBS Ltd., Surrey, UK). The IC50 values for certain compounds against CYP2D6 and CYP3A4 are provided in Table 6. Table 6 1 Assayed as a mixture of trans isomers (cyclopropyl). 2 Assayed as a mixture of cis isomers (cyclopropyl). EXAMPLE 19: Protocol for testing activity of compounds against hERG. The objective of these studies was to examine the in vitro effects of compounds on the hERG (human ether-a-go-go-related gene) channel current (a surrogate for I _Kr , the rapidly activating delayed rectifier cardiac potassium current; see, e.g., Redfern et al., Cardiovascular Research (2003) 58(1):32- 45). The concentration-response relationship for certain compounds on the hERG potassium channel current was evaluated at room temperature in stably transfected mammalian cells that express cloned hERG potassium channels, encoded by the KCNH2 gene. The hERG potassium channels were expressed in Chinese Hamster’s Ovary (CHO) cells that lack endogenous I _Kr . The cardiac potassium channel hERG is responsible for a rapid delayed rectifier current (I _Kr ) in human ventricles. Inhibition of I _Kr is the most common cause of cardiac action potential prolongation by non-cardiac drugs (see, e.g., Brown and Rampe, Pharmaceutical News (2000) 7:15- 20; Weirich and Antoni, Basic Res. Cardiol. (1998) 93 Suppl 1:125-132; Yap and Camm, Clin Exp. Allergy (1999) 29 Suppl 3:174-181). Increased action potential duration causes prolongation of the QT interval and is associated with torsade de pointes (see, e.g., Brown and Rampe, Pharmaceutical News (2000) 7:15-20). hERG positive control: Stock solutions of the positive control article were prepared in DMSO and stored at room temperature. CHO/hERG Cell Line: CHO Culture: CHO cells were stably transfected with hERG cDNA. Stable transfectants were maintained in the culture medium with the appropriate selection pressure and antibiotics. Test Method: 1. Cell Treatments: All experiments were performed at room temperature. Each cell was treated as its own control. Full block was achieved with the addition of 20µM Verapamil. Test Article Treatment Groups, 6-point dose response curve is generated.1:4 serial dilutions were made from the top concentration of 12µM. 2. Automated Patch Clamp Procedure a. Platform: For all hERG testing, the 384-well based automated Patch Clamp System SyncroPatch 384PE from Nanion Technologies with PatchControl software (data acquisition) and DataControl software (data analysis) was used. The recordings were performed at room temperature (22°C) on planar NPC-384 multi-hole chips with 4 holes per well at a medium resistance. b. The recordings were executed in whole cell patch mode. The composition of the internal solution was: 10 mM EGTA, 10 mM HEPES, 10 mM KCl, 10 mM NaCl and 110 mM KF, pH 7.2, mOsm = 285. The composition of the external solution was: 10 mM HEPES, 80 mM NaCl, 60 mM NMDG, 5 mM Glucose, 4 mM KCl, 5 mM CaCl2 and 1 mM MgCl2, pH 7.4, mOsm = 298. c. Compound preparation: All compounds were solvated in 100% DMSO. At the day of the experiment, a serial dilution in DMSO was prepared manually. The pre-diluted compounds were further diluted into external solution with a dilution factor of 1:500 (0.2% DMSO by volume). d. Compound acquisition mode: Single application of compounds was used with concentrations across the chip. Every well received once compound concentration followed by a full block of Verapamil to assess the leak current. Different concentrations of each compound to generate individual dose response relationships were spread across the chip. e. Onset and block of hERG current was measured using a stimulus voltage pattern consisting of a 500ms prepulse to -40mV (leakage subtraction), a 2-second activating pulse to +40mV followed by a 2-second test pulse to -40mV followed by a 2-second test pulse to -40mV. The pulse pattern was repeated continuously at 6 s intervals from a holding potential of -80 mV. Peak tail current was calculated from the current amplitude evoked by the -40 mV prepulse and subtracted from the total membrane current record. A small hyperpolarizing voltage step from -80 to -90 mV was implemented during holding potential to calculate the resistance according to Ohm’s law for quality control. 3. Data Analysis Data was stored on the Neurocrine Biosciences computer network for off-line analysis. Data acquisition and analysis was performed using Nanion Data Control software. Steady state is defined by the limiting constant rate of change with time (linear time dependence). The steady state before and after test article application was used to calculate percentage of current inhibited at each concentration. The IC ₅₀ values for certain compounds against hERG are provided in Table 7. Table 7 1 Assayed as a mixture of trans isomers (cyclopropyl). 2 Assayed as a mixture of cis isomers (cyclopropyl). The various embodiments described above can be combined to provide further embodiments. All U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications, and non-patent publications referred to in this specification and/or listed in the Application Data Sheet are incorporated herein by reference in their entirety. Aspects of the embodiments can be modified, if necessary, to employ concepts of the various patents, applications, and publications to provide yet further embodiments. These and other changes can be made to the embodiments in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.