Aminotetralin activators of serotonin receptors

Abstract

Described herein are compounds of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15 and their pharmaceutically acceptable salts, deuterated form, or stereoisomers, as well as their uses (e.g., as serotonin receptor agonists).

Description

PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699AMINOTETRALIN ACTIVATORS OF SEROTONIN RECEPTORSCROSS-REFERENCE TO RELEATED APPLCATION

[0001] The present Application claims priority to U.S. Provisional Application No. 63 / 690,260 filed September 3, 2024, and which is hereby incorporated by reference in its entirety.BACKGROUND

[0002] Rapid and effective treatments for stress-related disorders, such as depression, anxiety and post-traumatic stress disorder, remain a significant unmet medical need. Studies in humans and animals have shown that depression and stress exposure induce structural and functional changes in the brain. Signs of neuronal atrophy have been found in brain regions involved in stress-related behaviors, including prefrontal cortex and hippocampus. In animals, these structural changes have been shown to include loss of neurites, dendritic spines and synaptic contacts, as well as reduced hippocampal neurogenesis. Studies in humans and animals also have shown that depression and stress exposure decrease cerebral cortex and hippocampal levels of brain-derived neurotrophic factor (BDNF), which promotes neuronal survival and synaptic plasticity. Together, these findings are consistent with the hypothesis that reduced BDNF may play a role in stress-related neuronal structural changes. In support of this hypothesis, chronic but not acute administration of typical antidepressant drugs, such as selective serotonin (5-HT) reuptake inhibitors (SSRIs), attenuate the effects of stress on neurogenesis, neuronal structure and BDNF levels in animals and demonstrate antidepressant and anxiolytic effects in humans. In addition, single administration of ketamine attenuates these effects of stress in animals and demonstrates rapid-acting antidepressant effects in humans. Thus, compounds that promote the generation and / or maintenance of neurites, spines, synapses and / or neurons upon single administration may have rapid therapeutic benefit in the treatment of stress-related disorders.

[0003] Tryptamines are a structural class of compounds containing an indolealkylamine backbone with reported psychedelic and non-psychedelic effects. Psychedelic tryptamines include compounds such as psilocybin, its active metabolite psilocin, and N,N- dimethyltryptamine (DMT). Psilocybin and psilocin are found in hundreds of species of hallucinogenic mushrooms and were used in Aztec rituals. DMT is present in ayahuasca, a hallucinogenic brew traditionally used in ceremonial settings in South America. Psilocybin and ayahuasca have been reported to induce rapid and lasting clinical antidepressant efficacyPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 following single administration. Data in rodents and nonhuman primates also suggest the potential for antidepressant-like effects of psilocybin, DMT or ayahuasca. These compounds exert functional activity at a variety of central nervous system receptors, including serotonin receptors, of which partial agonism at 5-HT2A receptors is believed to mediate the psychedelic effects. Psychedelic tryptamines have been reported to exhibit neuronal plasticity-promoting effects, including neuritogenesis, spinogenesis, synaptogenesis, hippocampal cell proliferation and / or hippocampal neurogenesis, which may underlie their therapeutic benefit in the treatment of stress-related disorders, such as depression. Specifically, psilocin and DMT were reported to significantly increase measures of neurite outgrowth in primary embryonic rat cortical neurons. There is published data on the effects of the reference 5-HT2A agonist, DOI, and antagonist, M100907, in NGF-induced neurite outgrowth in rat adrenal medulla pheochromocytoma-derived PC12 cells.

[0004] There is a need for novel pharmaceutical compositions for the treatment of stress- related disorders. Given the reported 5-HT2A receptor agonist activity and ability to promote neurite outgrowth associated with classical psychedelic compounds novel compounds may provide an improved therapeutic index for treating stress related disorders with reduced side effect profiles.SUMMARY

[0005] In embodiments, the present disclosure provides a compound of Formula (I):

[0006] or a pharmaceutically acceptable salt thereof, wherein:

[0007] each Ri is independently H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;

[0008] R.2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, halogen, -CN, -ORe, -SRe, -S(O)(Y)R6, wherein Y is =0 or =NH;

[0009] R4 and Rs are independently H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl;

[0010] Re is H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl; and

[0011] w is 1, 2, or 3.

[0012] In embodiments, the present disclosure provides a compound of Formula (II):PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0013] or a pharmaceutically acceptable salt thereof, wherein:

[0014] each Ri is independently -H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;

[0015] R2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, halogen, -CN, -ORe, -SRe, -S(O)(Y)Re, wherein Y is =0 or =NH;

[0016] R4 and Rs are independently H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;

[0017] Re is H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl; and

[0018] w is 1, 2, or 3.

[0019] In embodiments, the present disclosure provides a compound of Formula (III):

[0020] or a pharmaceutically acceptable salt thereof, wherein:

[0021] Ri is independently H or optionally substituted Ci-Ce alkyl;

[0022] R2 and R.3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce alkenyl, halogen, -CN, -OR6, -SRe, -NO2, -S(O)(Y)R6, -(Ci-C6alkyl)-0-(Co-C6alkyl), A or -(CH2)-A, wherein Y is =0 or =NH;

[0023] R4 is H or optionally substituted Ci-Ce alkyl;

[0024] Rs is H, optionally substituted Ci-Ce alkyl, -(Ci-Ce alkylene)-OH, -(Ci-Ce alkylene)-O-(Ci-C6alkyl), -(Co-C6alkylene)-C(O)-OH, -(Co-C6alkylene)-C(O)-O-(Ci-C6alkyl), -(Ci-Ce alkyl ene)-O-C(O)-(Ci-Ce alkyl), -C(NRI)-N(RI)2, -(Co-C6alkylene)-S(O)(Y)Re, A or (Ci alkylene)- A, wherein Y is =0 or =NH;

[0025] or R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic or heterobicyclic ring, wherein the heterocyclic ring is optionally substituted with 1-3 RA or with A;

[0026] A is a monocyclic or bicyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl group, optionally substituted by 1-4 RA, wherein RA is optionally substituted Ci-Ce alkyl, halogen, oxo, -CN, -N(Re)2, -ORe, or SRe;PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0027] Re is H, or optionally substituted Ci-Ce alkyl;

[0028] m is 0 or 1;

[0029] 72 is 1, 2 or 3;

[0030] p is 1 or 2; and

[0031] wherein each alkyl or alkenyl group is optionally substituted

[0032] In embodiments, the present disclosure provides a compound of Formula (IV):

[0033] or a pharmaceutically acceptable salt thereof, wherein:

[0034] Ri is independently H or optionally substituted Ci-Ce alkyl;

[0035] R4 is H or optionally substituted Ci-Ce alkyl;

[0036] Rs is H, optionally substituted Ci-Ce alkyl, -(Ci-Ce alkylene)-OH, -(Ci-Ce alkylene)-O-(Ci-C6alkyl), -(Co-C6alkylene)-C(O)-OH, -(Co-C6alkylene)-C(O)-O-(Ci-C6alkyl), -(Ci-C6alkylene)-O-C(O)-(Ci-C6alkyl), -C(NRI)-N(RI)2, -(Co-C6alkylene)-S(O)(Y)Re, A or (Ci alkylene)- A, wherein Y is =0 or =NH;

[0037] or R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic or heterobicyclic ring, wherein the heterocyclic ring is optionally substituted with 1-3 RA or with A;

[0038] A is a monocyclic or bicyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl group, optionally substituted by 1-4 RA, wherein RA is optionally substituted Ci-Ce alkyl, halogen, oxo, -CN, -N(Re)2, -ORe, or SRe;

[0039] Re is H, or optionally substituted Ci-Ce alkyl;

[0040] m is 0 or 1;

[0041] 72 is 1, 2 or 3;

[0042] p is 1 or 2; and

[0043] wherein each alkyl or alkenyl group is optionally substituted.

[0044] In embodiments, the present disclosure provides compounds of Formula (V):Rio (V)PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0045] or a pharmaceutically acceptable salt thereof, wherein:

[0046] Rs, R9, and Rio are each independently -H or -alkyl;

[0047] (1) Rn and R12 are each independently -H, -alkyl, -alkylene-OH, -alkylene-O-alkyl, - alkylene-C(O)-OH, -alkylene-C(O)-O-alkyl, -alkylene-O-C(O)-alkyl, -C(NRi3)-N(Ri3)2, or - C(NRi3)-N(Ri3)2;

[0048] (2) Rn and R12 together with the nitrogen to which they are attached form a - heterocyclyl or -heteroaryl; or

[0049] (3) Rn is -aryl, -cycloalkyl, -heterocyclyl, heteroaryl, -alkylene-aryl, -alkylenecycloalkyl, -alkylene-heterocyclyl, or -alkyene-heteroaryl, and R12 is -H, -alkyl, -alkylene-OH, -alkylene-O-alkyl, -alkylene-C(O)-OH, -alkylene-C(O)-O-alkyl, -alkylene-O-C(O)-alkyl, - C(NRi3)-N(Ri3)2, or -C(NRi3)-N(Ri3)2;

[0050] R13 is -H or -alkyl;

[0051] m is 0 or 1;

[0052] n is 1, 2 or 3; and

[0053] p is 1 or 2;

[0054] wherein the compound is not:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0055] In embodiments, the present disclosure provides compounds of Formula (VI):

[0056] or a pharmaceutically acceptable salt thereof, wherein:

[0057] R13 and Ri4 are each independently -H or -alkyl;

[0058] Ris and Ri6 are each independently -H, -halo, -S(O)2Ri7, -alkyl, -cycloalkyl, -haloalkyl,-CN, -ORi8, -SRi8, -heteroalkyl, -heteroaryl, or -heterocyclyl;

[0059] R17 is -alkyl or -haloalkyl;

[0060] Ris is -H, alkyl, or -haloalky; and

[0061] Ring A is -heterocyclyl,

[0062] wherein the compound is not:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0063] In embodiments, the present disclosure provides compounds of Formula (VII):

[0064] or a pharmaceutically acceptable salt thereof, wherein:

[0065] R20 and R21 are each independently -H or -alkyl;

[0066] R22 and R23 are each independently -H, -halo, -S(O)2R26, -alkyl, -cycloalkyl, -haloalkyl,-CN, -OR27, -SR27, -heteroalkyl, -heteroaryl, -alkylene-O-alkyl, or -heterocyclyl; and

[0067] R24 and R25 are each independently -H, -alkylene-heterocyclyl, -heterocyclyl, - alkylene-aryl, -aryl, -alkylene-heteroaryl, or -heteroaryl,

[0068] wherein one of R24 and R25 is -alkylene-heterocyclyl, -heterocyclyl, -alkylene-aryl, - aryl, -alkylene-heteroaryl, or -heteroaryl;

[0069] R26 is -alkyl or -haloalkyl; and

[0070] R27is -H, alkyl, or -haloalky,

[0071] wherein the compound is not:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0072] In embodiments, the present disclosure provides compounds of Formula (VIII):

[0073] or a pharmaceutically acceptable salt thereof, wherein:

[0074] R28 and R29 are each independently -H or -alkyl;

[0075] R30 and R31 are each independently -H, branched -alkyl, -haloalkyl, -alkylene-S(O)2-R32, -alkylene-O-R33, -alkylene-(O)-OR33, or -alkylene-O-R32;

[0076] wherein at least one of R30 and R31 is not -H;

[0077] R32 is -alkyl or -haloalkyl;

[0078] R33 is -H, -alkyl, or -haloalkyl;

[0079] wherein the compound is not:

[0080] In embodiments, the present disclosure provides pharmaceutical compositions comprising a compound disclosed herein, and a pharmaceutically acceptable excipient.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0081] In embodiments, the present disclosure provides methods of activating a serotonin receptor in a subject or a biological sample comprising administering the compound disclosed herein or contacting the biological sample with the compound disclosed herein.

[0082] In embodiments, the present disclosure provides uses of the compound disclosed herein in the manufacture of a medicament for activating a serotonin receptor in a subject or a biological sample.

[0083] In embodiments, the present disclosure provides compounds disclosed herein for use in activating a serotonin receptor in a subject or a biological sample.

[0084] In embodiments, the present disclosure provides methods of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to the subject a compound disclosed herein.

[0085] In embodiments, the present disclosure provides uses of a compound disclosed herein in the manufacture of a medicament for treating or preventing a disease or disorder in a subject in need thereof.

[0086] In embodiments, the present disclosure provides compounds disclosed herein for use in treating or preventing a disease or disorder in a subject in need thereof.BRIEF DESCRIPTION OF THE DRAWINGS

[0087] FIG. 1 shows EC50 profiles of compounds comparing 5-HT2A and 5-HT2B selectivity

[0088] FIG. 2 shows EC50 profiles of compounds comparing 5-HT2A Gq and P-arrestin signaling.

[0089] FIG. 3 shows in vitro screening results using human 5-HT2AR (A) & 5-HT2BR (B) receptor IP1 accumulation HTRF assays guiding structural activity relationship (SAR) understanding across multiple chemical series.

[0090] FIG. 4 shows brain penetration profiles in rodents of select compounds following IP administration to male C57BL / 6 mice and SD rats.

[0091] FIG. 5 shows head-twitch measurement results after mice dosing with select compounds

[0092] FIG. 6 shows forced swim test results in mice injected with test compounds

[0093] FIG. 7 shows REM sleep test results in rats exhibiting depression-like phenotypes.DETAILED DESCRIPTION

[0094] Throughout this disclosure, various patents, patent applications and publications are referenced. The disclosures of these patents, patent applications and publications in theirPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 entireties are incorporated into this disclosure by reference for all purposes in order to more fully describe the state of the art as known to those skilled therein as of the date of this disclosure. This disclosure will govern in the instance that there is any inconsistency between the patents, patent applications and publications cited and this disclosure.Definitions

[0095] For convenience, certain terms employed in the specification, examples and claims are collected here. Unless defined otherwise, all technical and scientific terms used in this disclosure have the same meanings as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0096] Certain compounds described herein comprise one or more asymmetric centers, and thus can exist in various isomeric forms, e.g., enantiomers and / or diastereomers. For example, the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer. Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric synthesis. See, for example, Jacques et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen et al., Tetrahedron 33:2725 (1977); Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions p. 268 (E.F. Eliel, Ed., Univ, of Notre Dame Press, Notre Dame, IN 1972).

[0097] The term "about" when immediately preceding a numerical value means a range (e.g., plus or minus 10% of that value). For example, "about 50" can mean 45 to 55, "about 25,000" can mean 22,500 to 27,500, etc., unless the context of the disclosure indicates otherwise, or is inconsistent with such an interpretation. For example, in a list of numerical values such as "about 49, about 50, about 55, ... ", "about 50" means a range extending to less than half the interval(s) between the preceding and subsequent values, e.g., more than 49.5 to less than 50.5. Furthermore, the phrases "less than about" a value or "greater than about" a value should be understood in view of the definition of the term "about" provided herein. Similarly, the term "about" when preceding a series of numerical values or a range of values (e.g., "about 10, 20, 30" or "about 10-30") refers, respectively to all values in the series, or the endpoints of the range.

[0098] The terms "administer," "administering" or "administration" as used herein refer to administering a compound or pharmaceutically acceptable salt of the compound or aPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 composition comprising the compound or pharmaceutically acceptable salt of the compound to a patient.

[0099] The term “pharmaceutically acceptable salts” includes both acid and base addition salts. Pharmaceutically acceptable salts include those obtained by reacting the active compound functioning as a base, with an inorganic or organic acid to form a salt, for example, salts of hydrochloric acid, sulfuric acid, phosphoric acid, methanesulfonic acid, camphorsulfonic acid, oxalic acid, maleic acid, succinic acid, citric acid, formic acid, hydrobromic acid, benzoic acid, tartaric acid, fumaric acid, salicylic acid, mandelic acid, carbonic acid, etc. Base addition salts include but are not limited to, ethylenediamine, N-methyl-glucamine, lysine, arginine, ornithine, choline, N,N'-dibenzylethylenediamine, chloroprocaine, diethanolamine, procaine, N-benzylphenethylamine, diethylamine, piperazine, tris-(hydroxymethyl)-aminomethane, tetramethylammonium hydroxide, triethylamine, dibenzylamine, ephenamine, dehydroabietylamine, N-ethylpiperidine, benzylamine, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, ethylamine, basic amino acids, e. g., lysine and arginine dicyclohexylamine and the like. Examples of metal salts include lithium, sodium, potassium, magnesium, calcium salts and the like. Examples of ammonium and alkylated ammonium salts include ammonium, methylammonium, dimethylammonium, trimethylammonium, ethylammonium, hydroxyethylammonium, diethylammonium, butylammonium, tetramethylammonium salts and the like. Examples of organic bases include lysine, arginine, guanidine, diethanolamine, choline and the like. Those skilled in the art will further recognize that acid addition salts may be prepared by reaction of the compounds with the appropriate inorganic or organic acid via any of a number of known methods.

[0100] The term "treating" as used herein with regard to a patient, refers to improving at least one symptom of the patient's disorder. Treating can be improving, or at least partially ameliorating a disorder or an associated symptom of a disorder.

[0101] The terms "effective amount" and "therapeutically effective amount" are used interchangeably in this disclosure and refer to an amount of a compound, or a salt thereof, (or pharmaceutical composition containing the compound or salt) that, when administered to a patient, is capable of performing the intended result. The "effective amount" will vary depending on the active ingredient, the state, disorder, or condition to be treated and its severity, and the age, weight, physical condition and responsiveness of the mammal to be treated.

[0102] The term "therapeutically effective" applied to dose or amount refers to that quantity of a compound or pharmaceutical composition that is sufficient to result in a desired clinical benefit after administration to a patient in need thereof.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0103] The term “carrier” or “vehicle” as used interchangeably herein encompasses carriers, excipients, adjuvants, and diluents or a combination of any of the foregoing, meaning a material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material involved in carrying or transporting a pharmaceutical agent from one organ, or portion of the body, to another organ or portion of the body. In addition to the adjuvants, excipients and diluents known to one skilled in the art, the carrier includes nanoparticles of organic and inorganic nature.

[0104] When a range of values is listed, it is intended to encompass each value and sub-range within the range. For example, “Ci-Ce alkyl” is intended to encompass Ci, C2, C3, C4, Cs, Ce, C1-6, C1-5, Ci-4, C1-3, C1-2, C2-6, C2-5, C2-4, C2-3, C3-6, C3-5, C3-4, C4-6, C4-5, and C5-6 alkyl.

[0105] “Alkyl” or “alkyl group” refers to a fully saturated, straight or branched hydrocarbon chain having from one to twelve carbon atoms, and which is attached to the rest of the molecule by a single bond. Alkyls comprising any number of carbon atoms from 1 to 12 are included. An alkyl comprising up to 12 carbon atoms is a C1-C12 alkyl, an alkyl comprising up to 10 carbon atoms is a C1-C10 alkyl, an alkyl comprising up to 6 carbon atoms is a Ci-Ce alkyl and an alkyl comprising up to 5 carbon atoms is a C1-C5 alkyl. A C1-C5 alkyl includes Cs alkyls, C4 alkyls, C3 alkyls, C2 alkyls and Ci alkyl (z.e., methyl). A Ci-Ce alkyl includes all moieties described above for C1-C5 alkyls but also includes Ce alkyls. A C1-C10 alkyl includes all moieties described above for C1-C5 alkyls and Ci-Ce alkyls, but also includes C7, Cs, C9 and C10 alkyls. Similarly, a C1-C12 alkyl includes all the foregoing moieties, but also includes C11 and C12 alkyls. Non-limiting examples of C1-C12 alkyl include methyl, ethyl, zz-propyl, z-propyl, ec-propyl, zz-butyl, z-butyl, sec-butyl, / -butyl, zz-pentyl, / -amyl, zz-hexyl, zz-heptyl, zz-octyl, n- nonyl, zz-decyl, zz-undecyl, and zz-dodecyl. In embodiments, an alkyl group can be optionally substituted.

[0106] “Alkenyl” or “alkenyl group” refers to a straight or branched hydrocarbon chain having from two to twelve carbon atoms and having one or more carbon-carbon double bonds. Each alkenyl group is attached to the rest of the molecule by a single bond. Alkenyl group comprising any number of carbon atoms from 2 to 12 are included. An alkenyl group comprising up to 12 carbon atoms is a C2-C12 alkenyl, an alkenyl comprising up to 10 carbon atoms is a C2-C10 alkenyl, an alkenyl group comprising up to 6 carbon atoms is a C2-C6 alkenyl and an alkenyl comprising up to 5 carbon atoms is a C2-C5 alkenyl. A C2-C5 alkenyl includes Cs alkenyls, C4 alkenyls, C3 alkenyls, and C2 alkenyls. A C2-C6 alkenyl includes all moieties described above for C2-C5 alkenyls but also includes Ce alkenyls. A C2-C10 alkenyl includes all moieties described above for C2-C5 alkenyls and C2-C6 alkenyls, but also includes C7, Cs, C9 and C10PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 alkenyls. Similarly, a C2-C12 alkenyl includes all the foregoing moi eties, but also includes C11 and C12 alkenyls. Non-limiting examples of C2-C12 alkenyl include ethenyl (vinyl), 1 -propenyl, 2-propenyl (allyl), iso-propenyl, 2-methyl-l -propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1- pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5- hexenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 1-octenyl, 2- octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 1-nonenyl, 2-nonenyl, 3- nonenyl, 4-nonenyl, 5-nonenyl, 6-nonenyl, 7-nonenyl, 8-nonenyl, 1-decenyl, 2-decenyl, 3- decenyl, 4-decenyl, 5-decenyl, 6-decenyl, 7-decenyl, 8-decenyl, 9-decenyl, 1 -undecenyl, 2- undecenyl, 3-undecenyl, 4-undecenyl, 5-undecenyl, 6-undecenyl, 7-undecenyl, 8-undecenyl, 9-undecenyl, 10-undecenyl, 1-dodecenyl, 2-dodecenyl, 3-dodecenyl, 4-dodecenyl, 5- dodecenyl, 6-dodecenyl, 7-dodecenyl, 8-dodecenyl, 9-dodecenyl, 10-dodecenyl, and 11- dodecenyl. In embodiments, an alkyl group can be optionally substituted.

[0107] “Aryl” refers to a hydrocarbon ring system comprising hydrogen, 6 to 18 carbon atoms and at least one aromatic ring, and which is attached to the rest of the molecule by a single bond. For purposes of this disclosure, the aryl can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include fused or bridged ring systems. Aryls include, but are not limited to, aryls derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, c / .s-indacene, -indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. In embodiments, the “aryl” can be optionally substituted.

[0108] “Heteroaryl” refers to a 5- to 20-membered ring system comprising hydrogen atoms, one to nineteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, at least one aromatic ring, including compounds with aromatic resonance structures (e.g., 2-pyridone), and which is attached to the rest of the molecule by a single bond. For purposes of this disclosure, the heteroaryl can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include fused or bridged ring systems; and the nitrogen, carbon or sulfur atoms in the heteroaryl can be optionally oxidized; the nitrogen atom can be optionally quaternized. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzofuranyl, benzooxazolyl, benzothiadiazolyl, benzo[b][l,4]dioxepinyl, 1,4 benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodi oxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotri azolyl, benzo[4,6]imidazo[l,2 a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl,PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 oxadiazolyl, 2 oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1 oxidopyrimidinyl, 1- oxidopyrazinyl, 1-oxidopyridazinyl, 1 phenyl 1H pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e. thienyl). In embodiments, a heteroaryl group can be optionally substituted. “Heteroarylene” refers to a divalent radical derived from “heteroaryl”.

[0109] “Heterocyclyl”, “heterocyclic ring”, or “heterocycle” refers to a stable saturated, unsaturated, or aromatic 3- to 20-membered ring which consists of two to nineteen carbon atoms and from one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and which is attached to the rest of the molecule by a single bond. Heterocyclyl or heterocyclic rings include heteroaryls, heterocyclylalkyls, heterocyclylalkenyls, and hetercyclylalkynyls. Unless stated otherwise specifically in the specification, the heterocyclyl can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which can include fused, bridged, or spirocyclic ring systems; and the nitrogen, carbon or sulfur atoms in the heterocyclyl can be optionally oxidized; the nitrogen atom can be optionally quaternized; and the heterocyclyl can be partially or fully saturated. Examples of such heterocyclyl include, but are not limited to, dioxolanyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. In embodiments, a heterocyclyl or heterocyclylene group can be optionally substituted. “Heterocyclylene” refers to a divalent radical derived from “heterocyclyl”, “heterocyclic ring”, or “heterocycle”.

[0110] “Cycloalkyl” refers to a stable non-aromatic monocyclic or polycyclic fully saturated hydrocarbon consisting solely of carbon and hydrogen atoms, which can include fused, bridged, or spirocyclic ring systems, having from three to twenty carbon atoms (e.g., having from three to ten carbon atoms) and which is attached to the rest of the molecule by a single bond. Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyls include, for example, adamantyl, norbornyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, and the like. Unless otherwise stated specifically in the specification, a cycloalkyl group can be optionally substituted.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0111] “Haloalkyl” refers to an alkyl, as defined above, that is substituted by one or more halo radicals, e.g., trifluoromethyl, difluoromethyl, tri chloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, and the like. In embodiments, a haloalkyl group can be optionally substituted.

[0112] “Carbocyclyl,” “carbocyclic ring” or “carbocycle” refers to a rings structure, wherein the atoms which form the ring are each carbon, and which is attached to the rest of the molecule by a single bond. Carbocyclic rings can comprise from 3 to 20 carbon atoms in the ring. Carbocyclic rings include aryls and cycloalkyl, cycloalkenyl, and cycloalkynyl as defined herein. In embodiments, a carbocyclyl group can be optionally substituted.

[0113] The term “substituted” used herein means any of the groups described herein (e.g., alkyl, alkenyl, alkynyl, alkoxy, aryl, aralkyl, carbocyclyl, cycloalkyl, cycloalkenyl, cycloalkynyl, haloalkyl, heterocyclyl, and / or heteroaryl) wherein at least one hydrogen atom is replaced by a bond to a non-hydrogen atoms such as, but not limited to: a halogen atom such as F, Cl, Br, and I; an oxygen atom in groups such as hydroxyl groups, alkoxy groups, and ester groups; a sulfur atom in groups such as thiol groups, thioalkyl groups, sulfone groups, sulfonyl groups, and sulfoxide groups; a nitrogen atom in groups such as amines, amides, alkylamines, dialkylamines, arylamines, alkylarylamines, diarylamines, N-oxides, imides, and enamines; a silicon atom in groups such as trialkylsilyl groups, dialkylarylsilyl groups, alkyldiarylsilyl groups, and triarylsilyl groups; and other heteroatoms in various other groups. “Substituted” also means any of the above groups in which one or more hydrogen atoms are replaced by a higher-order bond (e.g., a double- or triple-bond) to a heteroatom such as oxygen in oxo, carbonyl, carboxyl, and ester groups; and nitrogen in groups such as imines, oximes, hydrazones, and nitriles. For example, “substituted” includes any of the above groups in which one or more hydrogen atoms are replaced with -NRgRh, -NRgC(=O)Rh, -NRgC(=O)NRgRh, -NRgC(=O)ORh, -NRgSO2Rh, -OC(=O)NRgRh, -ORg, -SRg, -SORg, -SChRg, -OSO2Rg, -SO2ORg, =NSO2Rg, and -SO2NRgRh. “Substituted” also means any of the above groups in which one or more hydrogen atoms are replaced with -C(=O)Rg, -C(=O)ORg, -C(=O)NRgRh, -CH2SO2Rg, -CH2SO2NRgRh. In the foregoing, Rgand Rh are the same or different and independently hydrogen, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, thioalkyl, aryl, aralkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclyl, A-heterocyclyl, heterocyclylalkyl, heteroaryl, A-heteroaryl and / or heteroarylalkyl. “Substituted” further means any of the above groups in which one or more hydrogen atoms are replaced by a bond to an amino, cyano, hydroxyl, imino, nitro, oxo, thioxo, halogen, alkyl, alkenyl, alkynyl, alkoxy, alkylamino,PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 thioalkyl, aryl, aralkyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkyl, haloalkyl, haloalkenyl, haloalkynyl, heterocyclyl, V-heterocyclyl, heterocyclylalkyl, heteroaryl, N- heteroaryl and / or heteroarylalkyl group. In embodiments, “substituted” further means any alkyl, cycloalkyl or heterocyclylalkyl in which one or more hydrogen atoms is replaced by an isotope e.g., deuterium.

[0114] These and other exemplary substituents are described in more detail in the Detailed Description, Examples, and claims. The invention is not intended to be limited in any manner by the above exemplary listing of substituents.Compounds

[0115] In an aspect of the present disclosure, a 5-HT2A serotonin receptor activator is provided, wherein the 5-HT2A serotonin receptor activator is a compound of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt, a stereoisomer, or a deuterated form thereof.

[0116] In embodiments, the present disclosure provides a compound of Formula (I):

[0117] or a pharmaceutically acceptable salt thereof, wherein:

[0118] each Ri is independently H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;

[0119] R.2 and Rs are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, halogen, -CN, -ORe, -SRe, -S(O)(Y)Re, wherein Y is =0 or =NH;

[0120] R4 and Rs are independently H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;

[0121] Re is H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl; and

[0122] n is 1, 2, or 3.

[0123] In embodiments, the present disclosure provides a compound of Formula (I-A):PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0124] or a pharmaceutically acceptable salt thereof, wherein:

[0125] each Ri is independently H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;

[0126] R2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, halogen, -CN, -ORe, -SRe, -S(O)(Y)Re, -heteralkyl, -heteroaryl, heterocyclyl, -cycloalkyl, - aryl, or -alkylene-aryl, wherein Y is =0 or =NH;

[0127] R4 and Rs are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, cycloalkyl, heteroalkyl, or heterocyclyl;

[0128] Re is H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl; and

[0129] w is 1, 2, or 3.

[0130] In embodiments, the present disclosure provides a compound of Formula (II):

[0131] or a pharmaceutically acceptable salt thereof, wherein:

[0132] each Ri is independently -H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;

[0133] R2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, halogen, -CN, -ORe, -SRe, -S(O)(Y)Re, wherein Y is =0 or =NH

[0134] R4 and Rs are independently H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;

[0135] Re is H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl; and

[0136] w is 1, 2, or 3.

[0137] In embodiments, the present disclosure provides a compound of Formula (II-A):PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0138] or a pharmaceutically acceptable salt thereof, wherein:

[0139] each Ri is independently H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;

[0140] R2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, halogen, -CN, -ORe, -SRe, -S(O)(Y)Re, -heteralkyl, -heteroaryl, heterocyclyl, -cycloalkyl, - aryl, or -alkylene-aryl, wherein Y is =0 or =NH;

[0141] R4 and Rs are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, cycloalkyl, heteroalkyl, or heterocyclyl;

[0142] Re is H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl; and

[0143] w is 1, 2, or 3.

[0144] In embodiments, each Ri is identical.

[0145] In embodiments, each Ri is independently optionally substituted C1-C3 alkyl or C1-C3 fluoroalkyl.

[0146] In embodiments, each Ri is independently optionally substituted Ci alkyl or Ci fluoroalkyl.

[0147] In embodiments, Ri is -CH3.

[0148] In embodiments, R2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci- Ce fluoroalkyl, halogen, -CN, -ORe, or -S(O)2Re.

[0149] In embodiments, at least one of R2 and R3 is H.

[0150] In embodiments, one of R2 and R3 is H.

[0151] In embodiments, R2 and R3 are independently H, -CH3, -(alkylene)CH3, - (alkylene)CH2F, -(alkylene)CHF2, -(alkylene)CF3, -CF3, F, Cl, Br, I, -CN, -OCH3, -S(O)2CH3, -S(O)2CH2F, -S(O)2CHF2, or -S(O)2CF3.

[0152] In embodiments, R2 and R3 are independently H, -CH3, -CF3, 1, or -CN.

[0153] In embodiments, each of R2 and R3 is H.

[0154] In embodiments, R4 and Rs are independently H, -CH3, -CH2CF3, -CH(CH3)2, or -CH2CH3.

[0155] In embodiments, at least one of R4 and Rs is H.

[0156] In embodiments, one of R4 and Rs is H.

[0157] In embodiments, R6is H, -CH3, -CH2CH3, -CF3, or -CH2CF3.

[0158] In embodiments, Re is independently H or -CH3.

[0159] In embodiments, n is 1 or 2.

[0160] In embodiments, n is 2.

[0161] In embodiments, the compound is a compound according to Table 1, or a pharmaceutically acceptable salt thereof.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0162] In embodiments, the present disclosure provides a compound of Formula (III):

[0163] or a pharmaceutically acceptable salt thereof, wherein:

[0164] Ri is independently H or optionally substituted Ci-Ce alkyl;

[0165] R2 and R.3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce alkenyl, halogen, -CN, -OR6, -SR6, -NO2, -S(O)(Y)R6, -(Ci-C6alkyl)-0-(Co-C6alkyl), A or -(CH2)-A, wherein Y is =0 or =NH;

[0166] R4 is H or optionally substituted Ci-Ce alkyl;

[0167] Rs is H, optionally substituted Ci-Ce alkyl, -(Ci-Ce alkylene)-OH, -(Ci-Ce alkylene)-O-(Ci-C6alkyl), -(Co-C6alkylene)-C(O)-OH, -(Co-C6alkylene)-C(O)-O-(Ci-C6alkyl), -(Ci-Ce alkyl ene)-O-C(O)-(Ci-Ce alkyl), -C(NRI)-N(RI)2, -(Co-C6alkylene)-S(O)(Y)Re, A or (Ci alkylene)- A, wherein Y is =0 or =NH;

[0168] or R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic or heterobicyclic ring, wherein the heterocyclic ring is optionally substituted with 1-3 RA or with A;

[0169] A is a monocyclic or bicyclic carbocyclyl, heterocycyl, aryl, or heteroaryl group, optionally substituted by 1-4 RA, wherein RA is optionally substituted Ci-Ce alkyl, halogen, oxo, -CN, -N(Re)2, -ORe, or SRe;

[0170] Re is H, or optionally substituted Ci-Ce alkyl;

[0171] m is 0 or 1;

[0172] 72 is 1, 2 or 3;

[0173] p is 1 or 2; and

[0174] wherein each alkyl or alkenyl group is optionally substituted.

[0175] In embodiments, the present disclosure provides a compound of Formula (III-A):

[0176] or a pharmaceutically acceptable salt thereof, wherein:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0177] Ri is independently H or optionally substituted Ci-Ce alkyl;

[0178] R2 and R.3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce alkenyl, halogen, -CN, -OR6, -SR6, -NO2, -S(O)(Y)R6, -(Ci-C6alkyl)-0-(Co-C6alkyl), A, -(CH2)-A, - heteroalkyl, -heteroaryl, heterocycyl, cycloalkyl, aryl, or alkylene-aryl, wherein Y is =0 or =NH;

[0179] R4 is H or optionally substituted Ci-Ce alkyl;

[0180] Rs is H, optionally substituted Ci-Ce alkyl, -(Ci-Ce alkylene)-OH, -(Ci-Ce alkylene)-O-(Ci-C6alkyl), -(Co-C6alkylene)-C(O)-OH, -(Co-C6alkylene)-C(O)-O-(Ci-C6alkyl), -(Ci-Ce alkyl ene)-O-C(O)-(Ci-C6alkyl), -C(NRI)-N(RI)2, -(Co-C6alkylene)-S(O)(Y)Re, A or (Ci alkylene)- A, wherein Y is =0 or =NH;

[0181] or R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic or heterobicyclic ring, wherein the heterocyclic ring is optionally substituted with 1-3 RA or with A;

[0182] A is a monocyclic or bicyclic carbocyclyl, heterocycyl, aryl, or heteroaryl group, optionally substituted by 1-4 RA, wherein RA is optionally substituted Ci-Ce alkyl, halogen, oxo, -CN, -N(Re)2, -ORe, or SRe;

[0183] Re is H, or optionally substituted Ci-Ce alkyl;

[0184] m is 0 or 1;

[0185] 72 is 1, 2 or 3;

[0186] p is 1 or 2; and

[0187] wherein each alkyl or alkenyl group is optionally substituted.

[0188] In embodiments, the compound is of Formula (III-B):pharmaceutically acceptable salt thereof.

[0189] In embodiments, the compound is of Formula (III-C):pharmaceutically acceptable salt thereof..

[0190] In embodiments, each Ri is identical.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0191] In embodiments, each Ri is independently unsubstituted C1-C3 alkyl or C1-C3 fluoroalkyl.

[0192] In embodiments, Ri is independently -CH3 or Ci fluoroalkyl.

[0193] In embodiments, Ri is -CH3.

[0194] In embodiments, one of R2, R3 and Rs is A or -(Ci alkylene)-A.

[0195] In embodiments, at least one of R2 and R3 is H.

[0196] In embodiments, one of R2 and R3 is H.

[0197] In embodiments, R2 and R3 are independently H, -OO-I(CH2)O-3CH3, -OO-I(CH2)O-3CH2F, -OO-I(CH2)O-3CHF2, -OO-I(CH2)O-3CF3, -OO-I(CH2)I-30H, -(CH2)O-30H-OO-I(CH2)I-3-0-(CH2)O-2CH3, F, Cl, Br, I, -CN, -OCH3, -S(O)2CH3, -S(O)2CH2F, -S(O)2CHF2, -S(O)2CF3, A or -(Cl alkylene)-A.

[0198] In embodiments, R2 and R3 are independently H, -CH3, F, Cl, Br, I, or -CN.

[0199] In embodiments, at least one of R2 and R3 is A or -(Ci alkylene)-A.

[0200] In embodiments, A is phenyl, cyclopropyl, or cyclobutyl.

[0201] In embodiments, R4 is H, -CH3, or -CH2CH3.

[0202] In embodiments, R4 is H.

[0203] In embodiments, Rs is H, -OO-I(CH2)O-3CH3, -OO-I(CH2)O-3CH2F, -OO-I(CH2)O-3CHF2, -OO-I(CH2)O-3CF3, -OO-I(CH2)I-30H, -(CH2)O-3OH -OO-I(CH2)I-3-0-(CH2)O-2CH3, F, Cl, Br, I, -CN, -OCH3, -S(O)2CH3, -S(O)2CH2F, -S(O)2CHF2, -S(O)2CF3, A or -(Ci alkylene)-A.

[0204] In embodiments, Rs is -CH2-A.

[0205] In embodiments, A is monocyclic carbocyclyl, heterocycyl, aryl, or heteroaryl.

[0206] In embodiments, A is phenyl, optionally substituted with 1-2 RA.

[0207] In embodiments, A is 3,5 disubstituted phenyl.

[0208] In embodiments, RA is -CH3, F, or Cl.

[0209] In embodiments, A is monocyclic carbocyclyl or heterocylcyl comprising 3-6 ring members.

[0210] In embodiments, A is fused bicyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl.

[0211] In embodiments, A is bicyclic, wherein A is phenyl substituted with phenyl or pyridinyl.

[0212] In embodiments, R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic to heterobicyclic ring, wherein the heterocyclic ring is optionally substituted with 1 or 2 RA.

[0213] In embodiments, R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic ring comprising 3-6 ring members.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0214] In embodiments, the heterocyclic ring is substituted by A

[0215] In embodiments, R4 and Rs come together with the nitrogen to which they are bound to form a heterobicyclic ring.

[0216] In embodiments, R4 and Rs come together with the nitrogen to which they are bound to form a pyrrolidinyl ring fused to a monocyclic aryl or monocyclic heteroaryl ring.

[0217] In embodiments, R4 and Rs come together with the nitrogen to which they are bound to form a pyrrolidinyl ring bound to a monocyclic aryl or monocyclic heteroaryl ring.

[0218] In embodiments, m is 0.

[0219] In embodiments, n is 1 or 2.

[0220] In embodiments, / ? is 1.

[0221] In embodiments, each alkyl or alkenyl group is optionally substituted by 1-3 R7, wherein R7 is independently CH3, fluoro, chloro, OH, or NH2, or wherein two R7 come together to form oxo.

[0222] In embodiments, the compound is a compound according to Table B, or a pharmaceutically acceptable salt thereof.

[0223] In embodiments, the present disclosure provides a compound of Formula (IV):

[0224] or a pharmaceutically acceptable salt thereof, wherein:

[0225] Ri is independently H or optionally substituted Ci-Ce alkyl;

[0226] R4 is H or optionally substituted Ci-Ce alkyl;

[0227] Rs is H, optionally substituted Ci-Ce alkyl, -(Ci-Ce alkylene)-OH, -(Ci-Ce alkylene)-O-(Ci-C6alkyl), -(Co-C6alkylene)-C(O)-OH, -(Co-C6alkylene)-C(O)-O-(Ci-C6alkyl), -(Ci-Ce alkyl ene)-O-C(O)-(Ci-C6alkyl), -C(NRI)-N(RI)2, -(Co-C6alkylene)-S(O)(Y)Re, A or (Ci alkylene)- A, wherein Y is =0 or =NH;

[0228] or R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic or heterobicyclic ring, wherein the heterocyclic ring is optionally substituted with 1-3 RA or with A;

[0229] A is a monocyclic or bicyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl group, optionally substituted by 1-4 RA, wherein RA is optionally substituted Ci-Ce alkyl, halogen, oxo, -CN, -N(Re)2, -ORe, or SRe;PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0230] Re is H, or optionally substituted Ci-Ce alkyl;

[0231] m is 0 or 1;

[0232] 72 is 1, 2 or 3;

[0233] p is 1 or 2; and

[0234] wherein each alkyl or alkenyl group is optionally substituted.

[0001] In embodiments, provided herein is a compound in Table 1, Table 2, or Table 3, or a pharmaceutically acceptable salt thereof.

[0002] In some embodiments, provided herein is a pharmaceutically acceptable salt of a compound in Table 1.

[0003] Table 1. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0235] In some embodiments, provided herein is a pharmaceutically acceptable salt of a compound in Table 2.

[0236] Table 2. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0237] In some embodiments, provided herein is a pharmaceutically acceptable salt of a compound in Table 3.

[0238] Table 3. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0239] In some embodiments, provided herein is a pharmaceutically acceptable salt of a compound in Table 4.

[0240] Table 4. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0241] In embodiments, the present disclosure provides compounds of Formula (V)

[0242] or a pharmaceutically acceptable salt thereof, wherein:

[0243] Rs, R9, and Rio are each independently -H or -alkyl;

[0244] (1) Rn and R12 are each independently -H, -alkyl, -alkylene-OH, -alkylene-O-alkyl, - alkylene-C(O)-OH, -alkylene-C(O)-O-alkyl, -alkylene-O-C(O)-alkyl, -C(NRi3)-N(Ri3)2, or - C(NRi3)-N(Ri3)2;

[0245] (2) Rn and R12 together with the nitrogen to which they are attached form a - heterocyclyl or -heteroaryl; or

[0246] (3) Rn is -aryl, -cycloalkyl, -heterocyclyl, heteroaryl, -alkylene-aryl, -alkylenecycloalkyl, -alkylene-heterocyclyl, or -alkyene-heteroaryl, and R12 is -H, -alkyl, -alkylene-OH,PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699-alkylene-O-alkyl, -alkylene-C(O)-OH, -alkylene-C(O)-O-alkyl, -alkylene-O-C(O)-alkyl, -C(NRI3)-N(RI3)2, or -C(NRi3)-N(Ri3)2;

[0247] R13 is -H or -alkyl;

[0248] m is 0 or 1;

[0249] n is 1, 2 or 3; and

[0250] p is 1 or 2;

[0251] wherein the compound is not:

[0252] In embodiments, Rs, R9, and Rio are each independently -H or -alkyl.

[0253] In embodiments, Rs, R9, and Rio are -H.

[0254] In embodiments, Rs, R9, and Rio are -alkyl.

[0255] In embodiments, Rs, R9, and Rio are -methyl.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0256] In embodiments, Rn and R12 are each independently -H, -alkyl, -alkylene-OH, - alkylene-O-alkyl, -alkylene-C(O)-OH, -alkylene-C(O)-O-alkyl, -alkylene-O-C(O)-alkyl, - C(NR13)-N(R13)2, Or -C(NR13)-N(R13)2.

[0257] In embodiments, R11 and R12 together with the nitrogen to which they are attached form a -heterocyclyl or -heteroaryl.

[0258] In embodiments, R11 is -aryl, -cycloalkyl, -heterocyclyl, heteroaryl, -alkylene-aryl, - alkylene-cycloalkyl, -alkylene-heterocyclyl, or -alkyene-heteroaryl, and R12 is -H, -alkyl, - alkylene-OH, -alkylene-O-alkyl, -alkylene-C(O)-OH, -alkylene-C(O)-O-alkyl, -alkylene-O- C(O)-alkyl, -C(NRi3)-N(Ri3)2, or -C(NRI3)-N(RI3)2.

[0259] In embodiments, R13 is -H or -alkyl. In embodiments, R13 is -H. In embodiments, R13 is -alkyl.

[0260] In embodiments, m is 0 or 1.

[0261] In embodiments, n is 1, 2, or 3.

[0262] In embodiments, p is 1 or 2.

[0263] In embodiments, the present disclosure provides compounds of Formula (V-A):

[0264] or a pharmaceutically acceptable salt thereof, wherein:

[0265] Ri, R2, and R3 are each independently -H or -alkyl;

[0266] (1) R4 and Rs are each independently -H or -alkyl; or

[0267] (2) R4 is -alkylene-aryl and Rs is -H.

[0268] In embodiments, the compounds of Formula (V) or (V-A) are one or more compounds of Table 5.

[0269] Table 5. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0270] In embodiments, the compounds of formula (V) or (V-A) are one or more compounds of Table 6.

[0272] In embodiments, the present disclosure provides compounds of Formula (VI):

[0274] or a pharmaceutically acceptable salt thereof, wherein:

[0275] R13 and Ri4 are each independently -H or -alkyl;

[0276] Ris and Ri6 are each independently -H, -halo, -S(O)2Ri7, -alkyl, -cycloalkyl, -haloalkyl,-CN, -ORi8, -SRi8, -heteroalkyl, -heteroaryl, or -heterocyclyl;

[0277] R17 is -alkyl or -haloalkyl;

[0278] Ris is -H, alkyl, or -haloalky; and

[0279] Ring A is -heterocyclyl,

[0280] wherein the compound is not:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0281] In embodiments, R13 and Ri4 are each independently -H or -alkyl.

[0282] In embodiments, R13 and Ri4 are -alkyl.

[0283] In embodiments, R13 and Ri4 are -H.

[0284] In embodiments, Ris and Ri6 are each independently -H, -halo, -S(O)2Ri7, -alkyl, - cycloalkyl, -haloalkyl, -CN, -ORis, -SRis, -heteroalkyl, -heteroaryl, or -heterocyclyl.

[0285] In embodiments, Ris and Ri6 are each independently -H, -halo, -S(O)2Ri7, -haloalkyl, - alkyl, or cycloalkyl.

[0286] In embodiments, Ring A is:

[0288] wherein:

[0289] q is 0, 1, 2, or 3; and

[0290] R19 is -H, -OH, -O-alkyl, -NH2, -NH(alkyl), -N(alkyl)2, -heterocyclyl, -aryl, or heteroaryl.PCT / US25 / 44749 03 September 2025 (03.09.2025)Attorney Docket No.: ATAI-115 / 01WO 338067-2699

[0291] In embodiments, Ring

[0292] In embodiments, Ring A is:

[0294] wherein:

[0295] Ring B is an -aryl or -heteroaryl.

[0298] In embodiments, Ring A is a 4 to 5 member -heterocyclyl.

[0299] In embodiments, the compounds of formula (VI) are one or more compounds of TablePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0301] In embodiments, the compounds of Formula (VI) are one or more compounds of Table 8.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0303] In embodiments, the present disclosure provides compounds of Formula (VII):

[0304] or a pharmaceutically acceptable salt thereof, wherein:

[0305] R20 and R21 are each independently -H or -alkyl;

[0306] R22 and R23 are each independently -H, -halo, -S(O)2R26, -alkyl, -cycloalkyl, -haloalkyl,-CN, -OR27, -SR27, -heteroalkyl, -heteroaryl, -alkylene-O-alkyl, or -heterocyclyl; and

[0307] R24 and R25 are each independently -H, -alkylene-heterocyclyl, -heterocyclyl, - alkylene-aryl, -aryl, -alkylene-heteroaryl, or -heteroaryl,

[0308] wherein one of R24 and R25 is -alkylene-heterocyclyl, -heterocyclyl, -alkylene-aryl, - aryl, -alkylene-heteroaryl, or -heteroaryl;

[0309] R26 is -alkyl or -haloalkyl; and

[0310] R27is -H, alkyl, or -haloalky,

[0311] wherein the compound is not:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0312] In embodiments, R20 and R21 are each independently -H or -alkyl.

[0313] In embodiments, R20 and R21 are -H.

[0314] In embodiments, R20 and R21 are -alkyl.

[0315] In embodiments, R22 and R23 are each independently -H, -halo, -S(O)2R26, -alkyl, - cycloalkyl, -haloalkyl, -CN, -OR27, -SR27, -heteroalkyl, -heteroaryl, -alkylene-O-alkyl, or - heterocyclyl.

[0316] In embodiments, R22 and R23 are each independently -H, -CN, or -halo.

[0317] In embodiments, R24 and R25 are each independently -H, -alkylene-heterocyclyl, - heterocyclyl, -alkylene-aryl, -aryl, -alkylene-heteroaryl, or -heteroaryl, wherein one of R24 and R25 is -alkylene-heterocyclyl, -heterocyclyl, -alkylene-aryl, -aryl, -alkylene-heteroaryl, or - heteroaryl;

[0318] In embodiments, one of R24 and R25 is -H and one of R24 and R25 is -alkylene- heterocyclyl, -heterocyclyl, -alkylene-aryl, -aryl, -alkylene-heteroaryl, or -heteroaryl.

[0319] In embodiments, one of R24 and R25 is -alkylene-aryl, -aryl, -alkylene-heteroaryl, or - heteroaryl.

[0320] In embodiments, one of R24 and R25 is

[0321] wherein:

[0322] r is 1 or 2; and

[0323] R28 is -O-alkyl, -OH, or -alkyl.

[0324] In embodiments, one of R24 and R25 isPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0325] In embodiments, the compounds of Formula (V) are one or more compounds of TablePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0327] In embodiments, the compounds of Formula (V) are one or more compounds of Table 10.

[0328] Table 10. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0329] In embodiments, the present disclosure provides compounds of Formula (VIII):

[0330] or a pharmaceutically acceptable salt thereof, wherein:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0331] R28 and R29 are each independently -H or -alkyl;

[0332] R30 and R31 are each independently -H, branched -alkyl, -haloalkyl, -alkylene-S(O)2- R32, -alkylene-O-R33, -alkylene-(O)-OR33, or -alkylene-O-R32;

[0333] wherein at least one of R30 and R31 is not -H;

[0334] R32 is -alkyl or -haloalkyl;

[0335] R33 is -H, -alkyl, or -haloalkyl;

[0336] wherein the compound is not:

[0337] In embodiments, R28 and R29 are each independently -H or -alkyl

[0338] In embodiments, R28 and R29 are -H.

[0339] In embodiments, R28 and R29 are -alkyl.

[0340] In embodiments, R30 and R31 are each independently -H, branched -alkyl, -haloalkyl, - alkylene-S(O)2-R32, -alkylene-O-R33, -alkylene-(O)-OR33, or -alkylene-O-R32;

[0341] In embodiments, R30 and R31 are each independently -haloalkyl, -alkylene-S(O)2-R32, - alkylene-O-R33, -alkylene-(O)-OR33, or -alkylene-O-R33.

[0342] In embodiments, the present disclosure provides compound of Formula (VIII-A):

[0343] or a pharmaceutically acceptable salt thereof, wherein:

[0344] R28 and R29 are each independently -H or -alkyl;

[0345] R34 is -O-alkyl, -C(O)-OH, -S(O)2-alkyl, -OH, -O-alkyl, or -O-haloalkyl.

[0346] In embodiments, the compounds of formula (V) are one or more compounds of Table 11.

[0347] Table 11. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0348] In embodiments, the present disclosure provides compounds of Formula (IX):

[0349] or a pharmaceutically acceptable salt thereof, wherein:

[0350] R35 and R36 are -alkyl;

[0351] R37 and R38 are each independently -H, -halo, -S(O)2R4i, -S(O)(NH), -alkylene, -alkyl,-cycloalkyl, -haloalkyl, -CN, -OR42, -SR42, -heteroalkyl, -heteroaryl, -heterocyclyl, -O-alkyl, - O-alkylene-aryl, -aryl, -O-haloalkyl, -NH2, -alkylene -cycloalkyl, -alkylene-OH, or -NO2;

[0352] wherein at least one of R37 and R38 is not -H;

[0353] R39 and R40 are each independently -H, -haloalkyl, -alkylene-O-alkyl, -C(=NH)-NH2, or -alkyl;

[0354] R41 is -alkyl or -haloalkyl; and

[0355] R42 is -H, -alkyl, or haloalkyl;

[0356] wherein the compound is not:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0357] In embodiments, R35 and R36 are -alkyl.

[0358] In embodiments, R35 and R36 are -methyl.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0359] In embodiments, R37 and R38 are each independently -H, -halo, -S(O)2R4i, -S(O)(=NH), -alkyl, -cycloalkyl, -haloalkyl, -CN, -OR42, -SR42, -heteroalkyl, -heteroaryl, -heterocyclyl, -O- alkyl, -O-alkylene-aryl, -aryl, -O-haloalkyl, -NH2, -alkylene -cycloalkyl, -alkylene-OH, or - NO2.

[0360] In embodiments, R37 and R38 are each independently -halo, -CF3, -S(O)2-Me, -CH2- CH-(CH3)2, -CH2-CH3, -CH-(CH3)2, -cyclopropyl, -S(O)2-CF3, -S(O)(=NH), -O-methyl, - CH2CH2CH2CF3, -CH2CH2CH2CH3, -CH2CH2CH2CHF2, -CH2CH2CH2CH2F, -cyclopentyl, - O-CF3, O-CHF2, -NH2, -CH2CH2CH2CH2-OH, -CH2-CH(OH)-CH2-CH3, or -NO2, wherein at least one of R37 and R38 is not -H.

[0361] In embodiments, R39 and R40 are each independently -H, -haloalkyl, -alkylene-O-alkyl, -C(=NH)-NH2, or -alkyl.

[0362] In embodiments, R39 and R40 are -H.

[0363] In embodiments, R39 and R40 are each independently -H and -alkyl.

[0364] In embodiments, R41 is -alkyl or -haloalkyl.

[0365] In embodiments, R42 is -H, -alkyl, or haloalkyl;

[0366] In embodiments, R39 and R40 are each independently -H and -haloalkyl.

[0367] In embodiments, the compounds of Formula (IX) are one or more compounds of Table 12.

[0368] Table 12. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0369] In embodiments, the compounds of Formula (IX) are one or more compounds of Table 13.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0370] Table 13. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0371] In embodiments, the present disclosure provides compounds of Table 14.

[0372] Table 14. Various compounds of the present disclosure

[0373] In embodiments, the present disclosure provides compounds of Table 15.

[0374] Table 15. Various compounds of the present disclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699Pharmaceutically acceptable salts

[0375] In embodiments, the compounds disclosed herein exist as their pharmaceutically acceptable salts. In embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts. In embodiments, the methods disclosed herein include methods of treating diseases by administering such pharmaceutically acceptable salts as pharmaceutical compositions.

[0376] In embodiments, the compounds described herein possess acidic or basic groups and therefor react with any of a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt. In embodiments, these salts are prepared in situ during the final isolation and purification of the compounds disclosed herein, or by separately reacting a purified compound in its free form with a suitable acid or base, and isolating the salt thus formed.

[0377] Examples of pharmaceutically acceptable salts include those salts prepared by reaction of the compounds described herein with a mineral, organic acid, or inorganic base, such salts including acetate, acrylate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, bisulfite, bromide, butyrate, butyn-l,4-dioate, camphorate, camphorsulfonate, caproate, caprylate, chlorobenzoate, chloride, citrate, cyclopentanepropionate, decanoate, digluconate,PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 dihydrogenphosphate, dinitrobenzoate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptanoate, glycerophosphate, glycolate, hemisulfate, heptanoate, hexanoate, hexyne- 1,6-dioate, hydroxybenzoate, y-hydroxybutyrate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, iodide, isobutyrate, lactate, maleate, malonate, methanesulfonate, mandelate metaphosphate, methanesulfonate, methoxybenzoate, methylbenzoate, monohydrogenphosphate, 1-napthalenesulfonate, 2-napthalenesulfonate, nicotinate, nitrate, palmoate, pectinate, persulfate, 3 -phenylpropionate, phosphate, picrate, pivalate, propionate, pyrosulfate, pyrophosphate, propiolate, phthalate, phenyl acetate, phenylbutyrate, propanesulfonate, salicylate, succinate, sulfate, sulfite, succinate, suberate, sebacate, sulfonate, tartrate, thiocyanate, tosylateundeconate, and xylenesulfonate.

[0378] Further, the compounds described herein can be prepared as pharmaceutically acceptable salts formed by reacting the free base form of the compound with a pharmaceutically acceptable inorganic or organic acid, including, but not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid metaphosphoric acid, and the like; and organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, p-toluenesulfonic acid, tartaric acid, trifluoroacetic acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, arylsulfonic acid, methanesulfonic acid, ethanesulfonic acid, 1,2- ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 2- naphthalenesulfonic acid, 4-methylbicyclo-[2.2.2]oct-2-ene-l -carboxylic acid, glucoheptonic acid, 4,4’-methylenebis-(3-hydroxy-2-ene-l-carboxylic acid), 3 -phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and muconic acid.

[0379] In embodiments, those compounds described herein which comprise a free acid group react with a suitable base, such as the hydroxide, carbonate, bicarbonate, or sulfate of a pharmaceutically acceptable metal cation, with ammonia, or with a pharmaceutically acceptable organic primary, secondary, tertiary, or quaternary amine. Representative salts include the alkali or alkaline earth salts, like lithium, sodium, potassium, calcium, and magnesium, and aluminum salts and the like. Illustrative examples of bases include sodium hydroxide, potassium hydroxide, choline hydroxide, sodium carbonate, N+(CI-4 alkyl)4, and the like.

[0380] Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine, and thePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 like. It should be understood that the compounds described herein also include the quaternization of any basic nitrogen-containing groups they contain. In embodiments, water or oil-soluble or dispersible products are obtained by such quaternization.

[0381] Unless indicated otherwise, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof. The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art.Compositions

[0382] In embodiments, the compounds described herein (e.g., Formula (I), Formula (II), Formula (III), Formula (III- A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt) are administered without a pharmaceutically acceptable excipient. In embodiments, the compound described herein is combined with one or more pharmaceutically suitable or acceptable carriers (also referred to herein as one or more pharmaceutically suitable (or acceptable) excipients, physiologically suitable (or acceptable) excipients, or physiologically suitable (or acceptable) carriers) selected on the basis of a chosen route of administration and standard pharmaceutical practice as described, for example, in Remington: The Science and Practice of Pharmacy (Gennaro, 21stEd. Mack Pub. Co., Easton, PA (2005)).

[0383] In embodiments, the present disclosure provides for a composition comprising a compound as otherwise described herein in combination with one or more pharmaceutically acceptable excipient.

[0384] In embodiments, compounds of Formula (I), Formula (II), Formula (III), Formula (III- A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt or deuterated versions of the foregoing, may be used on their own but will generally be administered in the form of a pharmaceutical composition in which the Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt compound / salt (active ingredient) is in association with pharmaceutically acceptable adjuvant(s), diluents(s) or carrier(s). Conventional procedures for the selection and preparation of suitable pharmaceutical formulations are described in, for example, “Pharmaceuticals - The Science of Dosage Form Designs”, M. E. Aulton, Churchill Livingstone, 2nd Ed. 2002.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0385] Accordingly, the present disclosure provides pharmaceutical compositions comprising a compound described herein (e.g., a compound Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15), or a pharmaceutically acceptable salt, deuterated form, or stereoisomer thereof, and a pharmaceutically acceptable excipient.

[0386] Pharmaceutical compositions are administered in a manner appropriate to the disease to be treated (or prevented). An appropriate dose and a suitable duration and frequency of administration will be determined by such factors as the condition of the patient, the type and severity of the patient's disease, the particular form of the active ingredient, and the method of administration. In general, an appropriate dose and treatment regimen provides the composition(s) in an amount sufficient to provide therapeutic and / or prophylactic benefit (e.g., an improved clinical outcome, such as more frequent complete or partial remissions, or longer disease-free and / or overall survival, or a lessening of symptom severity. Optimal doses are generally determined using experimental models and / or clinical trials. The optimal dose depends upon the body mass, weight, or blood volume of the patient.

[0387] In embodiments, the pharmaceutical composition is formulated for oral, topical (including buccal and sublingual), rectal, vaginal, transdermal, parenteral, intrapulmonary, intradermal, intrathecal and epidural and intranasal administration. Parenteral administration includes intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. In embodiments, the pharmaceutical composition is formulated for intravenous injection, oral administration, inhalation, nasal administration, topical administration, or ophthalmic administration. In embodiments, the pharmaceutical composition is formulated for oral administration. In embodiments, the pharmaceutical composition is formulated for intravenous injection. In embodiments, the pharmaceutical composition is formulated as a tablet, a pill, a capsule, a liquid, an inhalant, a nasal spray solution, a suppository, a suspension, a gel, a colloid, a dispersion, a suspension, a solution, an emulsion, an ointment, a lotion, an eye drop, or an ear drop. In embodiments, the pharmaceutical composition is formulated as a tablet.Methods of Use

[0388] In embodiments, the present disclosure provides a method of activating a 5-HT2A serotonin receptor, the method comprising administering a therapeutically effective amount of a compound disclosed herein (e.g., a compound of Formula (I), Formula (II), Formula (III),PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15) as otherwise described herein or a composition as otherwise described herein to a subject in need thereof. In embodiments, the compound or composition is administered to the patient for an administration period.

[0389] In embodiments, the present disclosure provides methods of activating a serotonin receptor in a subject or a biological sample, comprising administering the compound disclosed herein (e.g., a compound of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt) to the subject or contacting the biological sample with the compound disclosed herein.

[0390] In embodiments, the present disclosure provides uses of the compound disclosed herein (e.g., a compound of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III- B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt) in the manufacture of a medicament for activating a serotonin receptor in a subject or a biological sample.

[0391] In embodiments, the present disclosure provides compounds disclosed herein (e.g., a compound of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt) for use in activating a serotonin receptor in a subject or a biological sample.

[0392] In embodiments, the present disclosure provides methods of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to the subject the compound disclosed herein (e.g., a compound of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt).

[0393] In embodiments, the present disclosure provides uses of a compound disclosed herein (e.g., a compound of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III- B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt)in the manufacture of a medicament for treating or preventing a disease or disorder in a subject in need thereof.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0394] In embodiments, the present disclosure provides compounds disclosed herein (e.g., a compound of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt) for use in treating or preventing a disease or disorder in a subject in need thereof.

[0395] In embodiments, the disease or disorder is mediated by a serotonin receptor.

[0396] In embodiments, the disease or disorder is mood / depressive disorder, bipolar disorder, anxiety disorder, psychotic or delirium disorder, schizophrenia, schizoaffective disorder, personality disorder, abuse or neglect disorder, tic disorder, neurocognitive disorder, neurodevelopmental disorder, learning disorder, disruptive mood regulation disorder, intermittent explosive disorder, antisocial personality disorder, conduct disorder, behavioral and psychological symptoms of dementia, depression, anxiety, post-traumatic stress disorder (PTSD), major depressive disorder (MDD), treatment-resistant depression (TRD), substance use disorder (SUD), compulsive disorders, stress disorders, rumination, eating disorders, or a combination thereof.

[0397] In embodiments, the present disclosure provides methods of treating a mental health disease or disorder, the method comprising administering a compound of the present dislosure (e.g., a compound of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III- B), Formula (IV), Formula (V), Formula (V-A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt) and a pharmaceutically acceptable excipient.

[0398] In embodiments, the present disclosure provides methods of treating a mental health disease or disorder, the method comprising administering a pharmaceutical composition comprising a compound of the present dislosure (e.g., a compound of Formula (I), Formula (II), Formula (III), Formula (III-A), Formula (III-B), Formula (IV), Formula (V), Formula (V- A), Formula (VI), Formula (VII), Formula (VIII), Formula (VIII-A), Formula (IX), or Table 1-15, or a pharmaceutically acceptable salt) and a pharmaceutically acceptable excipient.

[0399] In embodiments, the mental health disease or disorder is selected from the group consisting of major depressive disorder, treatment resistant depression, substance use disorders and eating disorders. In embodiments, eating disorders include illnesses such as anorexia nervosa, bulimia nervosa, and other disorders related to eating (e.g., binge eating).

[0400] In embodiments, the mental health disease or disorder is an eating disorder.

[0401] In embodiments, the mental health disease or disorder is selected from the group consisting of compulsive disorders, anxiety disorders, stress disorders, and rumination.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0402] In embodiments, the mental health disease or disorder is a mood disorder. In embodiments, mood disorders include e.g., depressive disorders, such as major depressive disorder or treatment resistant depression.

[0403] In embodiments, the mental health disorder is a substance abuse disorder. In embodiments, substance use related disorders are disorders of maladaptive patterns of substance use, and include criteria, such as recurrent substance use related problems, tolerance to a substance, withdrawal upon discontinuing use, an inability to cut down or control use of the substance, and giving up important social, occupational, or recreational activities because of using the substance. See e.g., the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In embodiments, the substance use related disorder is a disorder resulting from the use of: alcohol; caffeine; cannabis; hallucinogens (such as phencyclidine or similarly acting arylcyclohexylamines, and other hallucinogens, such as LSD); inhalants; opioids; sedatives, hypnotics, or anxiolytics; stimulants (including amphetamine-type substances, cocaine, and other stimulants); tobacco; and other substances.NUMBERED EMBODIMENTS1. A compound of Formula (I):or a pharmaceutically acceptable salt thereof, wherein: each Ri is independently H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;R2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, halogen, -CN, -ORe, -SRe, -S(O)(Y)Re, wherein Y is =0 or =NH;R4 and Rs are independently H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl;Re is H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl; and n is 1, 2, or 3.2. A compound of Formula (II):PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699or a pharmaceutically acceptable salt thereof, wherein: each Ri is independently -H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;R2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, halogen, -CN, -ORe, -SRe, -S(O)(Y)Re, wherein Y is =0 or =NH;R4 and Rs are independently H, optionally substituted Ci-Ce alkyl, or Ci-Ce fluoroalkyl;Re is H, optionally substituted Ci-Ce, alkyl, or Ci-Ce fluoroalkyl; and n is 1, 2, or 3.3. The compound of embodiment 1 or embodiment 2, wherein each Ri is identical.4. The compound of any of embodiments 1-3, wherein each Ri is independently optionally substituted C1-C3 alkyl or C1-C3 fluoroalkyl.5. The compound of embodiment 4, wherein each Ri is independently optionally substituted Ci alkyl or Ci fluoroalkyl.6. The compound of embodiment 4 or embodiment 5, wherein Ri is -CH3.7. The compound of any of embodiments 1-6, wherein R2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce fluoroalkyl, halogen, -CN, -ORe, or -S(0)2Re.8. The compound of any of embodiments 1-6, wherein at least one of R2 and R3 is H.9. The compound of any of embodiments 1-6, wherein one of R2 and R3 is H.10. The compound of any of embodiments 7-9, wherein R2 and R3 are independently H,-CH3, -(alkylene)CH3, -(alkylene)CH2F, -(alkylene)CHF2, -(alkylene)CF3, -CF3, F, Cl, Br, I, - CN, -0CH3, -S(O)2CH3, -S(O)2CH2F, -S(O)2CHF2, or -S(O)2CF3.11. The compound of any of embodiments 7-10, wherein R2 and R3 are independently H, -CH3, -CF3, 1, or -CN.12. The compound of embodiment 7, wherein each of R2 and R3 is H.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-269913. The compound of any of embodiments 1-12, wherein R4 and Rs are independently H, -CH3, -CH2CF3, -CH(CH3)2, or -CH2CH3.14. The compound of any of embodiments 1-13, wherein at least one of R4 and Rs is H.15. The compound of any of embodiments 1-14, wherein one of R4 and Rs is H.16. The compound of any of embodiments 13, wherein each of R4 and Rs is H.17. The compound of any of embodiments 1-16, wherein Re is H, -CH3, -CH2CH3, -CF3, or -CH2CF3.18. The compound of embodiment 17, wherein Re is independently H or -CH3.19. The compound of any of embodiments 1-18, wherein n is 1 or 2.20. The compound of embodiment 19, wherein n is 2.21. A compound according to Table A.22. A compound of Formula (III):or a pharmaceutically acceptable salt thereof, wherein:Ri is independently H or optionally substituted Ci-Ce alkyl;R2 and R3 are independently H, optionally substituted Ci-Ce alkyl, Ci-Ce alkenyl, halogen, -CN, -OR6, -SRe, -NO2, -S(O)(Y)R6, -(Ci-C6alkyl)-0-(Co-C6alkyl), A or -(CH2)-A, wherein Y is =0 or =NH;R4 is H or optionally substituted Ci-Ce alkyl;Rs is H, optionally substituted Ci-Ce alkyl, -(Ci-Ce alkylene)-OH, -(Ci-Ce alkylene)-O-(Ci-C6alkyl), -(Co-C6alkylene)-C(O)-OH, -(Co-C6alkylene)-C(O)-O-(Ci-C6alkyl), -(Ci-C6alkylene)-O-C(O)-(Ci-C6alkyl), -C(NRI)-N(RI)2, -(Co-Ce alkylene)-S(O)(Y)Re, A or (Ci alkylene)-A, wherein Y is =0 or =NH;PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 or R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic or heterobicyclic ring, wherein the heterocyclic ring is optionally substituted with 1-3 RA or with A;A is a monocyclic or bicyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl group, optionally substituted by 1-4 RA, wherein RA is optionally substituted Ci-Ce alkyl, halogen, oxo, -CN, -N(Re)2, -ORe, or SRe;Re is H, or optionally substituted Ci-Ce alkyl; m is 0 or 1; n is 1, 2 or 3; p is 1 or 2; and wherein each alkyl or alkenyl group is optionally substituted.23. The compound of embodiment 22, wherein the compound is of Formula (Ill-a):pharmaceutically acceptable salt thereof.24. The compound of embodiment 22, wherein the compound is of Formula (Ill-b):pharmaceutically acceptable salt thereof.25. The compound of any of embodiment 22-24, wherein each Ri is identical.26. The compound of any of embodiments 22-25, wherein each Ri is independently unsubstituted C1-C3 alkyl or C1-C3 fluoroalkyl.27. The compound of embodiment 26, wherein Ri is independently -CH3 or Ci fluoroalkyl.28. The compound of embodiment 26, wherein Ri is -CH3.29. The compound of any of embodiments 22-28, wherein one of R2, R3 and Rs is A or -(Ci alkylene)-A.30. The compound of any of embodiments 22-29, wherein at least one of R2 and R3 is H.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-269931. The compound of any of embodiments 22-29, wherein one of R2 and R3 is H.32. The compound of any of embodiments 22-31, wherein R2 and R3 are independentlyH, -OO-I(CH2)O-3CH3, -OO-I(CH2)O-3CH2F, -OO-I(CH2)O-3CHF2,-OO-I(CH2)O-3CF3, -OO-I(CH2)I-30H, -(CH2)O-3OH -OO-I(CH2)I-3-0-(CH2)O-2CH3, F, Cl, Br,I, -CN, -OCH3, -S(O)2CH3, -S(O)2CH2F, -S(O)2CHF2, -S(O)2CF3, A or -(Ci alkylene)-A.33. The compound of embodiment 32, wherein R2 and R3 are independently H, -CH3, F, Cl, Br, I, or -CN.34. The compound of any of embodiments 22-32, wherein at least one of R2 and R3 is A or -(Ci alkylene)-A.35. The compound of embodiment 34, wherein A is phenyl, cyclopropyl, or cyclobutyl.36. The compound of any of embodiments 22-35, wherein R4 is H, -CH3, or -CH2CH3.37. The compound of any of embodiments 22-35, wherein R4 is H.38. The compound of any of embodiments 22-37, wherein Rs is H, -OO-I(CH2)O-3CH3,-OO-I(CH2)O-3CH2F, -OO-I(CH2)O-3CHF2, -OO-I(CH2)O-3CF3, -OO-I(CH2)I-30H, -(CH2)O-30H -OO-I(CH2)I-3-0-(CH2)O-2CH3, F, Cl, Br,I, -CN, -OCH3, -S(O)2CH3, -S(O)2CH2F, -S(O)2CHF2, -S(O)2CF3, A or -(Ci alkylene)-A.39. The compound of any of embodiments 22-25, wherein Rs is -CH2-A.40. The compound of embodiment 39, wherein A is monocyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl.41. The compound of embodiment 39, wherein A is phenyl, optionally substituted with 1- 2 RA.42. The compound of embodiment 41, wherein A is 3,5 disubstituted phenyl.43. The compound of embodiments 38-42, wherein RA is -CH3, F, or Cl.44. The compound of embodiment 39, wherein A is monocyclic carbocyclyl or heterocyclyl comprising 3-6 ring members.45. The compound of embodiment 39, wherein A is fused bicyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-269946. The compound of embodiment 39, wherein A is bicyclic, wherein A is phenyl substituted with phenyl or pyridinyl.47. The compound of any of embodiments 22-35, wherein R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic to heterobicyclic ring, wherein the heterocyclic ring is optionally substituted with 1 or 2 RA.48. The compound of embodiment 47, wherein R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic ring comprising 3-6 ring members.49. The compound of embodiment 48, wherein the heterocyclic ring is substituted by A.50. The compound of any of embodiments 22-35, wherein R4 and Rs come together with the nitrogen to which they are bound to form a heterobicyclic ring.51. The compound of embodiment 50, wherein R4 and Rs come together with the nitrogen to which they are bound to form a pyrrolidinyl ring fused to a monocyclic aryl or monocyclic heteroaryl ring.52. The compound of embodiment 50, wherein R4 and Rs come together with the nitrogen to which they are bound to form a pyrrolidinyl ring bound to a monocyclic aryl or monocyclic heteroaryl ring.53. The compound of any of embodiments 22-52, wherein m is 0.54. The compound of any of embodiments 22-53, wherein n is 1 or 2.55. The compound of any of embodiments 22-54, wherein p is 1.56. The compound of any of embodiments 22-55, wherein each alkyl or alkenyl group is optionally substituted by 1-3 R7, wherein R7 is independently CH3, fluoro, chloro, OH, or NH2, or wherein two R7 come together to form oxo.57. The compound of embodiment 22, wherein the compound is a compound according to Table B.58. A compound of Formula (IV):PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 or a pharmaceutically acceptable salt thereof, wherein:Ri is independently H or optionally substituted Ci-Ce alkyl;R4 is H or optionally substituted Ci-Ce alkyl;Rs is H, optionally substituted Ci-Ce alkyl, -(Ci-Ce alkylene)-OH, -(Ci-Ce alkylene)-O-(Ci-C6alkyl), -(Co-C6alkylene)-C(O)-OH, -(Co-C6alkylene)-C(O)-O-(Ci-C6alkyl), -(Ci-C6alkylene)-O-C(O)-(Ci-C6alkyl), -C(NRI)-N(RI)2, -(Co-Ce alkylene)-S(O)(Y)Re, A or (Ci alkylene)-A, wherein Y is =0 or =NH; or R4 and Rs come together with the nitrogen to which they are bound to form a heterocyclic or heterobicyclic ring, wherein the heterocyclic ring is optionally substituted with 1-3 RA or with A;A is a monocyclic or bicyclic carbocyclyl, heterocyclyl, aryl, or heteroaryl group, optionally substituted by 1-4 RA, wherein RA is optionally substituted Ci-Ce alkyl, halogen, oxo, -CN, -N(Re)2, -ORe, or SRe;Re is H, or optionally substituted Ci-Ce alkyl; m is 0 or 1; n is 1, 2 or 3; p is 1 or 2; and wherein each alkyl or alkenyl group is optionally substituted.59. A compound according to Table C.60. A pharmaceutical composition comprising the compound of any one of embodiments 1-59, and a pharmaceutically acceptable excipient.61. A method of inhibiting a serotonin receptor in a subject or a biological sample, comprising administering the compound of any one of embodiments 1-59 to the subject or contacting the biological sample with the compound of any one of embodiments 1-59.62. Use of the compound of any one of embodiments 1-59 in the manufacture of a medicament for inhibiting a serotonin receptor in a subject or a biological sample.63. A compound of any one of embodiments 1-59 for use in inhibiting a serotonin receptor in a subject or a biological sample.64. A method of treating or preventing a disease or disorder in a subject in need thereof, comprising administering to the subject a compound of any one of embodiments 1-59.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-269965. Use of a compound of any one of embodiments 1-59 in the manufacture of a medicament for treating or preventing a disease or disorder in a subject in need thereof.66. A compound of any one of embodiments 1-59 for use in treating or preventing a disease or disorder in a subject in need thereof.67. The method, use, or compound for use of any one of embodiments 64-66, wherein the disease or disorder is mediated by a serotonin receptor.68. The method, use, or compound for use of any one of embodiments 64-66, wherein the disease or disorder is mood / depressive disorder, bipolar disorder, anxiety disorder, psychotic or delirium disorder, schizophrenia, schizoaffective disorder, personality disorder, abuse or neglect disorder, tic disorder, neurocognitive disorder, neurodevelopmental disorder, learning disorder, disruptive mood regulation disorder, intermittent explosive disorder, antisocial personality disorder, conduct disorder, behavioral and psychological symptoms of dementia, depression, anxiety, post-traumatic stress disorder (PTSD), major depressive disorder (MDD), treatment-resistant depression (TRD), substance use disorder (SUD), compulsive disorders, stress disorders, rumination, eating disorders, or a combination thereof.EXAMPLES

[0404] The present disclosure is further illustrated by reference to the following Examples. However, it should be noted that these Examples, like the embodiments described above, are illustrative and are not to be construed as restricting the scope of the disclosure in any way.

[0405] LSD and other ergolines also act upon DI and D2 dopamine receptors and adrenergic receptors (Nichols, 2004). In particular, activation of 5- HT2A receptors located in cortical and subcortical structures of the brain are thought to mediate the subjective, behavioral and psychological effects of psychedelics in both animals and humans (Halberstadt et al, 2015; Preller, 2017; Preller, 2018, Kraehenmann, 2017a; Kraehenmann, 2017b; Vollenweider et al, 1998). In rodents, psychedelics have shown to elicit a ‘head twitch response’ which has been demonstrated to be a direct and selective consequence of 5-HT2A activation over other similar serotonin receptors including both 5-HT2C and 5-HT2B (Halberstatdt, 2015; Winter et al., 2007; Benneyworth et al., 2015; Titeler et al, 1988). Similar observations have been made in humans where the administration of ketanserin, a 5-HT2A receptor antagonist, blocked the majority of subjective effects induced by DMT, psilocyin and LSD (Preller, 2017; Preller, 2018; Kraehenmann, 2017a; Kraehenmann, 2017b; Vollenweider, 1988; Preller, 2016; Valle, 2016). In addition, psychedelic effects elicited by psilocybin have correlated with 5-HT2APCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 receptor occupancy as measured by positron emission tomography in the prefrontal cortex (PFC) and other cortical regions in humans (Madsen, 2019). While 5-HT2A is the predominant driver of psychedelic effects in humans, other serotonin receptors, like 5-HT1A, are likely contributing to the overall psychedelic experience including both visual and attentiondisrupting effects in humans (Pokorny et al., 2016; Carter et al., 2005).

[0406] Known psychedelics consist of three main molecular classes. The first class are indoleamines, including N,N-dimethyltryptamine (DMT), 5-methoxy-DMT (5-MeO-DMT), psilocybin and 4-hydroxy- DMT. The second class are phenylalkylamines, which include mescaline, as well as synthetic mescaline analogs including 2,5-dimethoxy-4- iodoamphetamine (DOI) and 2, 5 -dimethoxy -4-bromoamphetamine (DOB). The third class of are ergolines, such as LSD (Nichols, 2004; Vollenweider et al, 2020). The phenylalkylamines are selective agonists of 5- HT2 receptors, including 5- HT2A, 5- HT2B and 5-HT2C receptors (Halberstadt, 2015). The indoleamines and ergolines act as partial agonists of 5-HT1, 5-HT2, 5-HT6 and 5-HT7 receptors (Nichols, 2004).

[0407] Biased signaling consequences of 5-HT2A activation by various agonists strongly impact whether or not a compound will be hallucinogenic or non-hallucinogenic. For example, LSD and lisuride both activate the 5-HT2A receptor but in slightly different ways which result in the activation of different intracellular signaling cascades. LSD and lisuride have been shown to active canonical Gq-based signaling downstream of 5-HT2A, but only LSD stimulated the expression of early growth response proteins (EGR1 and EGR2) by activating Gi / o subunits and the SRC protein kinase (Gonzalez-Maeso et al, 2007). Differential functional selectivity has been shown for several phenalkylamine pyschedelics which were found to be biased 5-HT2A agonists (Pottie et al, 2020). The compounds, including 25H-NBF, 25H- NBMD, 25H-NBOH and 25H-NBOMe showed a statistically significant preference towards the recruitment of P-arrestin 2 over miniGaq, as compared to the reference psychedelic substance LSD. Differential biased agonism elicited across multiple classes of psychedelics warrants further investigation to identify whether this functional selectivity may provide compounds with greater selectivity, fewer side effects, greater neuroplastic effects and improved therapeutic benefit

[0408] Initial work studying aminotetralins as lysergic acid congeners demonstrated that while 2-amino-5,8-dimethoxy-6-methyl-l,2,3,4-terahydronaphthalene has activity at 5-HT receptors, the compound failed to elicit common psychedelic side effects in rats in comparison to mescaline or 2,5-dimethoxy-4-methylphenylisopropylamine at similar doses (Nichols et al, 1974). Additional drug discrimination studies in LSD-trained rats and MDMA-trained ratsPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 found that stimulus generalization did not occur with any of the 2-aminotetralins studied suggesting that consistent with previous studies the tetralin congeners are most likely not hallucinogenic (Nichols et al, 1990).

[0409] Unless otherwise noted, all materials / reagents were obtained from commercial suppliers and used without further purification. Reactions were monitored by LC-MS and / or thin layer chromatography (TLC) on silica gel 60 F254 (0.2mm) pre-coated aluminum foil or glass-backed and visualized using UV light.1HNMR (400 MHz) spectra was recorded on Broker spectrometers at RT with TMS or the residual solvent peak as the internal standard. The line positions or multiples are given in (5) and the coupling constants (J) are given as absolute values in Hertz (Hz). The multiplicities in1HNMR spectra are abbreviated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br or broad (broadened). Preparative HPLC purifications were performed on Shimadzu LC-6AD. All purification work was completed using a Shim-pack PREP-DDS(H)KIT Column. The mobile phases were water (with 0.1% HCO2H) and acetonitrile; all reagents used were of HPLC grade. The flow rate was lOml / min. LC-MS analyses were performed on Shimadzu LCMS-2020 equipped with LC- 20AD or 30AD pumps, SPD-M20A PDA and Alltech 3300 ELSD; Mobile Phase: A:Water (0.1% Formic acid), B: ACN; 5 minute run; Column: Sepax BR-C18 4.6*50mm,3um; Flow Rate: 1.0ml / min; Oven Temperature: 40°C; Gradient: 20% B for 0.2 min, increase to 70% B within 1.8 min, 70% B for 2.8 min, back to 20% B within 0.2 min, 20% B for 2 min). Preparative TLC was performed on Whatman LK6F Silica Gel 60A size 20x20 cm plates with a thickness of 1000 pm or equivalent.

[0410] Example 1: Synthetic Schemes

[0411] In general, the compounds of the present disclosure may be prepared according to one or more of the following Schemes:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699Method APCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699Method BPd(dba)21 ,1 ’-bis(diphenylphosphino)ferrocene 40-60 Co, 2h, N2Int 1PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699Method CScheme D, general aminationScheme D, general aminationPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0412] Synthesis of Compound 2:

[0413] A mixture of 1 (10 g, 80.9 mmol), EtiN (24.5 g, 242 mmol) and phthalic anhydride (24 g, 161 mmol) in toluene (50 mL) was stirred at 110°C overnight. The reaction was quenched with water (100 mL) at RT. The resulting mixture was extracted with EtOAc (3 x 100 mL), dried over anhydrous Na2SC>4 and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 10% to 100% gradient in 10 min; detector, UV 220 nm which afforded compound 1.1 (13 g, 74% yield) as a white solid. (ESI, m / z): [M+H]+=218.05. [a]D25-72.2 (c = 2 mg / mL, DCM)

[0414] Synthesis of compound 1.2PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699tris-(o-tolyl)phosphineEt3N, Pd(OAc)2, DMF1.2tris-(o-tolyl)phosphineEt3N, Pd(OAc)2, DMF1.1 1.2

[0415] A mixture of compound 1.1 (1.5 g, 6.91 mmol, 1 equiv.), 2-bromo-l,4- dimethoxybenzene (2.25 g, 10.35 mmol, 1.5 equiv.), P(o-tol)3 (630 mg, 2.07 mmol, 0.3 equiv.) and EtiN (2.1 g, 20.71 mmol, 3 equiv.) in DMF (50 mL) was added Pd(OAc)2 (155 mg, 0.69 mmol, 0.1 equiv.) at 25°C under nitrogen atmosphere. Then the mixture was stirred at 110°C overnight under nitrogen atmosphere. The reaction was quenched with water (100 mL) at room temperature. The resulting mixture was extracted with EtOAc (3 x 100 mL). The combined organic layers were washed with brine (100 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, MeCN in water (10 mmol / L NH4HCO3), 10% to 100% gradient in 10 min; detector, UV 254 nm. This resulted in compound 1.2 (600 mg, 24% yield) as a yellow oil.

[0416] (ESI, m / z): [M+H]+=354.05.

[0417] Synthesis of compound 1.3PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26991.2 1.3

[0418] A mixture of compound 1.2 (600 mg, 1.70 mmol, 1 equiv.) and 10% Pd / C (200 mg) in MeOH (6 mL) was stirred at room temperature for 1 h under 2 atm. hydrogen atmosphere. The resulting mixture was filtered and the filter cake was washed with MeOH (6 mL x 3). The filtrate was concentrated under reduced pressure to give compound 1.3 (580 mg, 96% yield) as a yellow oil, which was used in the next step directly without further purification.

[0419] (ESI, m / z): [M+H]+=356.15.

[0420] Synthesis of compound 1.4

[0421] A mixture of compound 1.3 (100 mg, 0.28 mmol, 1 equiv.) and TfOH (105 mg, 0.70 mmol, 2.5 equiv.) in chlorobenzene (1 mL) was stirred at 80°C for 30 min. After cooling, the mixture was basified to pH 9 with saturated NaHCOs (aq.). The resulting mixture was extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (30 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in water (10 mmol / L NH4HCO3),PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-269910% to 100% gradient in 10 min; detector, UV 220 nm. This resulted in compound 1.4 (50 mg, 52% yield, 95% purity) as a yellow solid.

[0422] (ESI, m / z): [M+H]+= 338.15.

[0423] Synthesis of compound 11.4 1

[0424] A mixture of compound 1.4 (50 mg, 0.15 mmol, 1 equiv.) and NH2NH2-H2O (18 mg, 0.37 mmol, 2.5 equiv.) in EtOH (1 mL) was stirred at 80°C for 1 h. The resulting mixture was filtered and the filter cake was washed with ethanol (2 x 10 mL). The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in water (10 mmol / L NH4HCO3), 10% to 100% gradient in 10 min; detector, UV 220 nm. This resulted in compound 1 (20 mg, 65% yield, 95% purity) as a white solid.

[0425] (ESI, m / z): [M+H]+= 208.15. [a]D25= -32 (c = 1 mg / mL, MeOH)

[0426] Synthesis of Compound 1.

[0427] Compound 1 was prepared identically to compound 2 but starting with R-isomer of the starting material.

[0428] Compound 1 and 2 were also prepared via ulternate methodsPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0429] STEP 1

[0430] To a solution of 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-one (500 mg, 2.424 mmol, 1.0 equiv) in tetrahydrofuran (5 mL) was added (R)-2-methylpropane-2-sulfinamide (440.75 mg, 3.636 mmol, 1.5 equiv) and tetraethoxytitanium (1.11 g, 4.848 mmol, 2 equiv). The mixture was stirred for 2 hours at 60°C under nitrogen atmosphere. Then, it was cooled to room temperature and used at next step directly. MS m / z [M+H]+(ESI):310.30.

[0431] STEP 2

[0432] The solution of the product from the previous step in tetrahydrofuran was cooled to OoC and was added NaBEU (101 mg, 1.1 equiv). The mixture was stirred for 2 hours at 0°C~rt. Then, it was quenched with methanol and water. The resulting mixture was filtered; the filter cake was washed with tetrahydrofuran. The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (0.1% NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 210 nm which afforded the product (1.5 g, 86%) as a yellow oil. The residue was purified by Prep-HPLC with the following conditions: Column:PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699YMC-Actus Triart C18 ExRS 30*150mm, Spun; Mobile Phase A: water (lOmmol / L NH4HCO3+0.1%NH3H2O), Mobile Phase B: MeCN; Flow rate: 60 mL / min; Gradient: 40% B to 53% B in lOmin; Wave Length: 254nm / 220nm; RTl(min): 82.3 / 8.85. providing the two diastereomers A, A (220 mg) and S, S (190 mg). MS m / z [M+H]+(ESI):312.15.

[0433] STEP 3

[0434] HC1 in 1,4-di oxane (4 mol / L, 8 mL) was added the R,R product from the previous step (50 mg, 0.161 mmol). The solution was stirred for 1 hour at RT. The resulting mixture was concentrated under reduced pressure. The residue was purified by trituration with diethyl ether which afforded the crude product. The residue was purified by Column: CHIRALPAK SS 2*25 cm, 5 pm; Mobile Phase A: HEX(0.1%DEA), Mobile Phase B: IPA; Flow rate: 20 mL / min; Gradient: isocratic 20; Wave Length: 220 / 254 nm; RTl(min): 18.714; RT2(min): 21.936; Sample Solvent: EtOH— HPLC; Injection Volume: 0.3 mL; Number of Runs: 29. The eluent was concentrated under reduced pressure. The residue was dissolved in HC1 in methanol and concentrated again under reduced pressure which afforded 1 (31 mg, 65%) as a grey solid. MS m / z [M+H]+(ESI):208.00. 'HNMR (400 MHz, Methanol^) d 6.74 (s, 2H), 3.77 (s, 3H), 3.76 (s, 3H), 3.50-3.42 (m, 1H), 3.24-3.16 (m, 1H), 3.03-2.92 (m, 1H), 2.72-2.60 (m, 1H), 2.60- 2.49 (m, 1H), 2.24-2.12 (m, 1H), 1.81-1.65 (m, 1H).

[0435] Preparation of Compounds 3 and 4

[0436] To a stirred solution of 2 (20 mg, 0.096 mmol) and I2 (36 mg, 0.144 mmol) in methanol (0.5 mL) was added Ag2SC>4 (45 mg, 0.144 mmol) in portions at RT under nitrogen. The mixture was stirred for 16 h. The resulting mixture was filtered, the filter cake was washed with methanol (2 x 4 mL). The filtrate was concentrated under reduced pressure and the crude product was purified by Prep-Chiral HPLC with the following conditions [Column: CHIRALPAK IG, 2*25 cm, 5 pm; Mobile Phase A: HEX(0.5% 2M NH3-MeOH), Mobile Phase B: ETOH; Flow rate: 20 mL / min; Gradient: isocratic 20; Wave Length: 220 / 254 nm; RTl(min): 8.333; RT2(min): 10.502; Sample Solvent: EtOH; Injection Volume: 0.5 mL; Number Of Runs: 12] to afford 3 and 4. Compound 3 (5. mg, 15%) as a brown solid. MS m / z [M+H]+(ESI):334.00. 'HNMR (400 MHz, Methanol^) d 6.99 (s, 1H), 3.66 (s, 3H), 3.60 (s,PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26993H), 3.09-2.90 (m, 2H), 2.81-2.68 (m, 1H), 2.49-2.30 (m, 2H), 2.00-1.87 (m, 1H), 1.50-1.35 (m, 1H). Compound 4 (3 mg, 9%) as a brown solid. MS m / z [M+H]+(ESI):334.05. 'H NMR (300 MHz, Methanol^) d 7.10 (s, 1H), 3.77 (s, 3H), 3.70 (s, 3H), 3.22-3.09 (m, 1H), 3.08- 2.95 (m, 2H), 2.82-2.66 (m, 1H), 2.40-2.22 (m, 1H), 2.10-1.97 (m, 1H), 1.65-1.48 (m, 1H).

[0437] Preparation of Compound 5

[0438] Compound 5 was prepared analoguesly to 4 and exhibited identical spectral properties to 4.

[0439] Preparation of Compounds 6 and 7PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0440] STEP 1

[0441] To a stirred solution of the mixture of iodo isomers (600 mg, 1.80 mmol) and phthalic anhydride (320 mg, 2.16 mmol) in toluene (30 mL) was added triethylamine (401 mg, 3.96 mmol) at RT. The resulting mixture was stirred for overnight at 110°C under nitrogen. The reaction was cooled to RT and water was added. The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with brine and dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. ThePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 residue was purified by silica gel column chromatography, eluted with petroleum ether / ethyl acetate (3: 1) to afford the protected amine (500 mg, 60%) as a yellow oil. MS m / z [M+H]+(ESI):464.05.

[0442] STEP 2

[0443] A solution of the product from step 1 (500 mg, 1.079 mmol) in NMP (10 mL) was treated with copper(I) iodide (411 mg, 2.158 mmol) and methyl 2,2-difluoro-2-sulfoacetate (829 mg, 4.316 mmol) at RT under nitrogen. The resulting mixture was stirred for overnight at 120°C under nitrogen. The resulting mixture was diluted with di chloromethane (90mL), washed with brine, dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (lOmmol / L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 254 nm.to afford the product (380 mg, 87%) as a yellow solid. MS m / z [M+H]+(ESI):406.15.

[0444] STEP 3

[0445] A solution of the product from step 2 (130 mg, 0.321 mmol) in ethyl alcohol (2.6 mL) was treated with hydrazine (75 mg, 2.343 mmol) at RT under nitrogen. The resulting mixture was stirred for 15 min at 80°C under nitrogen atmosphere. The reaction was cooled to room temperature, diluted with water and extracted with dichloromethane. The organic phase was collected and concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (0.1% NFE.EEOMOmmol / LNFLElCCh), 10% to 100% gradient in 15 min; detector, UV 210 nm which afforded the product (220 mg, 85%) as a yellow oil. MS m / z [M+H]+(ESI):276.1

[0446] STEP 4

[0447] A solution of of the product from step 3 (190 mg, 0.690 mmol) and 3-chloro-5- methylbenzaldehyde (96 mg, 0.621 mmol) in methanol (3.8 mL) was stirred for 30 minutes. Then diacetyl peroxide sodioboranyl acetate (731 mg, 3.450 mmol) was added to the solution at 0°C. The mixture was stirred for 16 hours. The resulting mixture was diluted with dichloromethane (60 mL), washed with brine, dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed- phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (lOmmol / L NH4HCO3), 10% to 100% gradient in 15 min; detector, UV 210 nm which afforded the crude product. The residue was purified by Column: GreenSep Nitro, 30*150mm 5um; Mobile Phase A: CO2, Mobile Phase B: EtOH(20mMNH3M); FlowPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 rate: 60 mL / min; Gradient: isocratic 30% B; Column Temperature(°C): 35; Back Pressure(bar): 100; Wave Length: 254 nm; RTl(min): 7.72; RT2(min): 10.00; Sample Solvent: MEOH; Injection Volume: 1 mL; Number Of Runs: 6.0 which afforded 6 and 7. Compound 6 (60 mg, 20%) as a light yellow oil. MS m / z [M+H]+(ESI):414.20. 'H NMR (300 MHz, Methanol-d4) 5 7.23 (s, 1H), 7.11 (d, J = 12.9 Hz, 2H), 6.89 (s, 1H), 3.89-3.77 (m, 5H), 3.74 (s, 3H), 3.23- 3.07 (m, 1H), 3.01-2.73 (m, 2H), 2.68-2.42 (m, 2H), 2.33 (s, 3H), 2.24-2.08 (m, 1H), 1.66-1.43 (m, 1H). Compound 7 (40 mg, 14%) as a light yellow oil. MS m / z [M+H]+(ESI):414.20. 'H NMR (300 MHz, Methanol^) d 7.22 (s, 1H), 7.12 (d, J= 12.3 Hz, 2H), 6.89 (s, 1H), 3.83 (s, 5H), 3.73 (s, 3H), 3.18-2.97 (m, 2H), 2.97-2.84 (m, 1H), 2.75-2.59 (m, 1H), 2.46-2.35 (m, 1H), 2.33 (s, 3H), 2.21-2.07 (m, 1H), 1.62-1.42 (m, 1H).

[0448] Compound 2 was sinilartly preapared according to step 3 and exhibited identical spectral properties as 1

[0449] Preaparation of Compounds 8 and 9

[0450] STEP 1

[0451] To a solution of protected amine from the preparation of compounds 6 and 7 (1.00 g, 2.16 mmol) in dioxane (15 mL) was added dimethyl sulfite (2.38 g, 21.6 mmol), dimethylsilyl ether (435 mg, 3.24 mmol), TBAB (696 mg, 2.16 mmol,) and palladium chloride; bis(triphenylphosphine) (15w mg, 0.22 mmol). The mixture was stirred for 16 hours at 120°C under nitrogen. The reaction was cooled to RT, diluted with DCM and washed with water. The organic phase was washed with brine, dried by anhydrous Na2SC>4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted withPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PE / EA (1 : 1) to afford the product (500 mg, 56%) as a yellow oil. MS m / z [M+H]+(ESI):416.11.

[0452] STEP 2

[0453] To a solution of the product from step 1 (200 mg, 0.48 mmol, 1.0) in ethanol (2 mL) was added NH2NH2 H2O (0.5 mL). The mixture was stirred for 15min at 80 °C under nitrogen. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in water (0.1% NH3 H2O+I Ommol / L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 220 nm. to afford the product as a mixture of isomers (110 mg, 80%) as a white solid. MS m / z [M+H]+(ESI):286.10. The isomers were separated by Prep-HPLC with the following conditions [Column: YMC-Actus Triart Cl 8 ExRS 30*150mm, 5pm; Mobile Phase A: water (lOmmol / L NH4HCO3+0.1%NH3H2O), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient: 54% B to 71% B in 9 min; Wave Length: 254nm / 220nm; RTl(min): 8.5] to afford 8 and 9. Compound 8 (6 mg, 15%) as a white solid. MS m / z [M+H]+(ESI):286.00.1H NMR (400 MHz, Methanol^) <57.11 (s, 1H), 3.77 (d, J= 0.8 Hz, 6H), 3.11 (s, 3H), 3.10-2.91 (m, 3H), 2.73-2.62 (m, 1H), 2.35-2.23 (m, 1H), 2.05-1.90 (m, 1H), 1.54-1.36 (m, 1H). Compound 9 (5.2 mg, 13.45%) as a white solid. MS m / z [M+H]+(ESI):286.00. 'H NMR (400 MHz, Methanol-^) 3 7.11 (s, 1H), 3.77 (d, J = 0.8 Hz, 6H), 3.19-3.02 (m, 5H), 2.94-2.83 (m, 1H), 2.64-2.51 (m, 1H), 2.50-2.40 (m, 1H), 2.05- 1.97 (m, 1H), 1.61-1.46 (m, 1H).

[0454] Preparation of Compounds 10 and 12

[0455] STEP 1

[0456] To a solution of iodo amine (400 mg, 1.201 mmol) in methylene chloride was added and di-tert-butyl dicarbonate (524 mg, 2.40 mmol), triethylamine (364 mg, 3.60 mmol) and 4- dimethylaminopyridine (29 mg, 0.24 mmol). The mixture was stirred for 3 h and diluted withPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 dichloromethane. The resulting mixture was washed with water and brine. The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (lOmmol / L NH4HCO3), 10% to 100% gradient in 20 min; detector, UV 210 nm which afforded the product (200 mg, 38%) as a brown solid. MS m / z [M+H]+(ESI):434.10.

[0457] STEP 2

[0458] To a solution of the product from step 1 (200 mg, 0.462 mmol) was added dicyclohexyl({2-[2,4,6-tris(propan-2-yl)phenyl]phenyl})phosphane (24 mg, 0.051 mmol) and (lZ,5Z)-cycloocta-l,5-diene; trimethyl-({[(trimethylsilyl)methyl]palladio}methyl)silane (18 mg, 0.046 mmol) in toluene (2 mL) under nitrogen. The mixture was then heated at 100°C for 1 min before adding silver (1+) ion (trifluoromethyl)sulfanide (125 mg, 0.601 mmol) and N,N,N-triethylanilinium iodide (183 mg, 0.601 mmol)and sealing the pressure vessel. After heating at 100°C for 16 h the resulting mixture was diluted with di chloromethane. The resulting mixture was washed with water and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (lOmmol / L NH4HCO3), 10% to 100% gradient in 20 min; detector, UV 210 nm which afforded the product (80 mg, 43%) as a yellow oil. MS m / z [M+H]+(ESI):408.15.

[0459] STEP 3

[0460] To a mixture of the product from step 2 (90 mg, 0.221 mmol) in acetonitrile (1.6 mL) / carbon tetrachloride (1.6 mL) / water (3.2 mL) was added tri chlororuthenium hydrate (1.99 mg, 0.009 mmol) and NalCh (189 mg, 0.884 mmol). The mixture was stirred for 2 hours at RT. The resulting mixture was diluted with dichloromethane and washed with water and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (0.1% NH3.H2O+ I Ommol / L NH4HCO3), 10% to 100% gradient in 20 min; detector, UV 210 nm wwhich afforded the product (55 mg, 57%) as a yellow oil. MS m / z [M+H]+(ESI):441.15.

[0461] STEP 4

[0462] T0 asolution of HC1 in 1,4-di oxane (4 mol / L, 2 mL) was added the predict from step 3 (55 mg, 0.125 mmol). The solution was stirred for 2 hours at RT. The resulting mixture was concentrated under reduced pressure. The crude product (50 mg) was purified by Prep-HPLC with the following conditions (Column: YMC-Actus Triart Diol -HILIC 3*25 cm, 5 pm; MobilePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699Phase A: CO2, Mobile Phase B: MeCN: MeOH=4: l(20mM NH3.M); Flow rate: 75 mL / min; Gradient: isocratic 44% B; Column Temperature(°C): 35; Back Pressure(bar): 100; Wave Length: 220 nm; RTl(min): 5.40; RT2(min): 6.10; Sample Solvent: MEOH; Injection Volume: 1 mL; Number Of Runs: 6.0) to afford compounds 10 and 12. Compound 10 (7 mg) as a light brown solid. MS m / z [M+H]+(ESI): 340.00.JH NMR (300 MHz, Methanol^) 5 7.21 (s, 1H), 3.87 (d, J = 7.2 Hz, 6H), 3.24-2.92 (m, 3H), 2.78-2.61 (m, 1H), 2.58-2.41 (m, 1H), 2.15-1.99 (m, 1H), 1.67-1.51 (m, 1H). Compound 12 (13 mg) as a yellow solid. MS m / z [M+H]+(ESI):339.95.XH NMR (400 MHz, Methanol-A) 57.27 (s, 1H), 3.89 (d, J= 18.0 Hz, 6H), 3.67- 3.53 (m, 1H), 3.36-3.28 (m, 1H), 3.18-3.09 (m, 1H), 2.95-2.82 (m, 1H), 2.73-2.59 (m, 1H), 2.33-2.20 (m, 1H), 1.87-1.72 (m, 1H).

[0463] Preparation of Compound 11

[0464] Compound 11 was prepared analoguesly to compound 3 beginning with the opposite enenatiomer and exhibited identitical spectal properties to 3.

[0465] Preparation of Compound 13

[0466] STEP 1

[0467] A solution of the protected amine (100 mg, 0.216 mmol) in DMF (1 mL) was treated with CuCN (48 mg, 0.540 mmol) at 150°C for 3h under nitrogen. The resulting mixture was extracted with EtOAc (3 x 5 mL). The combined organic layers were washed with H2O (5x5 mL) and dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The crude resulting mixture was used in the next step directly without further purification.

[0468] STEP 2

[0469] A solution of of the product from step 1 (31 mg, 0.086 mmol) in EtOH (1 mL) was treated with hydrazine monohydrate (20 mg, 0.40 mmol) at RT for 32 h. The residue was purified by Prep-HPLC with the following conditions: Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: MECN; Flow rate: 60 mL / min; Gradient: 3% B to 16% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 7.16 to afford 13 (15 mg, 75%) as a white solid. LCMS [M+H]+(ESI): 233. 'H NMR (300 MHz, Methanol-d4) 58.52 (s, 1H), 7.04 (s, 1H), 3.91 (s, 3H), 3.85 (s, 3H), 3.56-3.45 (m, 1H), 3.27-PCT / US25 / 44749 03 September 2025 (03.09.2025)Attorney Docket No.: ATAI-115 / 01WO 338067-26993.19 (m, 1H), 3.09-3.00 (m, 1H), 2.84-2.71 (m, 1H), 2.62-2.53 (m, 1H), 2.26-2.17 (m, 1H),1.82-1.69 (m, 1H).Preparation of Compound 14

[0470] Compound 14 was prepared analoguesly to compound 13 beginning with the opposite enantiomer and exhibited identitical spectal properties to 13.

[0471] Preparation of Compound 15

[0472] Compound 15 was prepared analoguesly to compound 13 beginning with the racemate of the iodoisiomers. The crude product was purified by Prep-Achiral-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: MeCN; Flow rate: 60 mL / min; Gradient: 2% B to 8% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 10.52 / 12.23) to afford 15 (11 mg) as a white solid. MS m / z [M+H]+(ESI):233.00. 'H NMR (300 MHz, Methanol-d4) 3 8.55 (s, 1H), 7.05 (s, 1H), 3.91 (s, 3H), 3.85 (s, 3H), 3.52-3.61 (m, 1H) 3.24 (dd, J= 17.6, 5.4 Hz, 1H), 3.14-2.97 (m, 1H), 2.87-2.68 (m, 1H), 2.57 (dd, J= 17.8, 9.7 Hz, 1H), 2.20 (s, 1H), 1.86-1.65 (m, 1H).

[0473] STEP 1

[0474] To a solution of 5 (300 mg, 0.812 mmol) in toluene (3 mL) was added phthalic anhydride (180 mg, 1.22 mmol) and EtsN (246 mg, 2.44 mmol). The mixture was stirred atPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699110°C overnight. The resulting solution was quenched with water (10 mL) and extracted with ethyl acetate (3 x 5 mL) and the organic layers were combined. The organic phase was washed with saturated aqueous sodium chloride (2 x 3 mL). The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 50% to 90% gradient in 20 min; detector, UV 220 nm. This resulted in the protected amine (180 mg, 47%) as a white solid.

[0475] STEP 2

[0476] To a solution of the product from step 1 (180 mg, 0.389 mmol) in NMP (2 mL) was added methyl 2,2-difhioro-2-sulfoacetate (149 mg, 0.778 mmol) and Cui (148 mg, 0.778 mmol). The mixture was stirred at 120 °C overnight. The resulting solution was quenched with water (10 mL) and extracted with ethyl acetate (3 x 5 mL). The combined organic phases were washed with saturated aqueous sodium chloride (2 x 2 mL). The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 50% to 90% gradient in 20 min; detector, UV 220 nm to afford the trifluoromethyl derivative (110 mg, 69%) as a white solid.

[0477] STEP 3

[0478] To a solution of the product from step 2 (110 mg, 0.271 mmol) in EtOH (2 mL) was added hydrazine hydrate (34 mg, 0.677 mmol). The resulting mixture was stirred for 1 hour at 80°C. The reaction mixture was cooled to RT. After filtration, the reaction mixture was concentrated in vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 10% to 50% gradient in 20 min; detector, UV 220 nm to afford 17 (60 mg, 80%) as a yellow solid.

[0479] STEP 4

[0480] To a solution of 17 (60 mg, 0.218 mmol) in THF (1 mL) and H2O (1 mL) was added BOC2O (52 mg, 0.240 mmol, 1.1) and NaHCCh (55 mg, 0.654 mmol). The mixture was stirred at RT for 2 hours under nitrogen. Water (3 mL) was added to the reaction mixture and then extracted with DCM (3 x 5 mL). The combined organic layers were washed with saturated NaCl (4 mL) and dried over sodium sulfate. Filtered and the filtrate was evaporated in vacuum to give a residue. The residue was purified by reversed-phase flash chromatography with thePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 20% to 80% gradient in 20 min; detector, UV 220 nm to afford the Boc protected product (60 mg, 73%) as a white solid.

[0481] STEP 5

[0482] To a solution of of the product of step 4 (30 mg, 0.080 mmol) in DMF (0.6 mL) was added NaH (4.8 mg, 0.120 mmol, 60% in mineral oil) at 0°C. Then CH3I (12 mg, 0.088 mmol) was added slowly at 0°C. The mixture was stirred at RT overnight under nitrogen. The reaction was quenched by saturated NEUCl aq. (3 mL) and then extracted with ethyl acetate (3 x 5 mL). The combined organic layers were washed with saturated NaCl aq. (5 mL) and dried over sodium sulfate. Filtered and the filtrate was evaporated in vacuum to give a residue. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 20% to 80% gradient in 20 min; detector, UV 220 nm to afford the methylated product (28 mg, 89%) as a white solid.

[0483] STEP 6

[0484] The product from step 5 (30 mg, 0.077 mmol) was dissolved in 4 M HC1 / dioxane (0.6 mL) and the mixture was stirred at RT for 2 h. After concentration, the resulting solution was purified by Prep-HPLC (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water / 0.1%HCl; Gradient (B%): 6% B to 25% B in 8 min; RTl(min): 10.2) to afford 19 (16 mg, 61%) as a white solid. [M+H]+(ESI):290.05. 'HNMR (300 MHz, methanol-d4) 5 6.98 (s, 1H), 3.87 (s, 3H), 3.76 (s, 3H), 3.58 - 3.43 (m, 1H), 3.36 - 3.32 (m, 1H), 3.20 - 3.13 (m, 1H), 2.82 (s, 4H), 2.69 - 2.56 (m, 1H), 2.41 - 2.29 (m, 1H), 1.84 - 1.65 (m, 1H).

[0485] Preparation of Compound 16

[0486] Compound 16 was prepared analogously to 17 starting 5 and exhibited identical spectral properties to 17.

[0487] Preparation of Compound 18

[0488] Compound 18 was prepared analogously to 19 (14 mg, 56%) as a white solid. [M+H]+(ESI):290.05. 'HNMR (300 MHz, Methanol-d4) 56.99 (s, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 3.58 - 3.39 (m, 1H), 3.34 (d, J = 5.6 Hz, 1H), 3.20 - 3.04 (m, 1H), 2.82 (s, 4H), 2.63 (dd, J = 17.5, 9.8 Hz, 1H), 2.44 - 2.29 (m, 1H), 1.85 - 1.66 (m, 1H).

[0489] Preparation of Compound 20PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0490] STEP 1

[0491] To a solution of of the Boc-protected amine (30 mg, 0.080 mmol) in DMF (0.3 mL) was added NaH (5 mg, 0.120 mmol, 60% in oil) at 0°C, followed by ethyl iodide (14 mg, 0.088 mmol). The mixture was stirred at RT for 2 h under nitrogen. The resulting solution was quenched with saturated NEUCl aq. (3 mL), extracted with ethyl acetate (3 x 10 mL) and the organic layers were combined. The resulting mixture was washed with saturated aqueous sodium chloride (5 mL). The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 50% to 90% gradient in 20 min; detector, UV 220 nm. to afford the product (28 mg, 86%) as a white solid. [M+H]+(ESI):464.

[0492] STEP 2

[0493] The product from step 1 (20 mg, 0.051 mmol) was dissolved in 4 M HC1 / dioxane (0.4 mL) and the mixture was stirred at RT for 2 h. After concentration, the resulting solution was purified by Prep-HPLC (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water / 0.1%FA, Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 12% B to 25% B in 8 min) to afford 20 (10 mg) as a white solid. [M+H]+(ESI):304.10.1H NMR (300 MHz, Methanol-d4) 5 6.98 (s, 1H), 3.87 (s, 3H), 3.76 (s, 3H), 3.54 (d, J= 16.0 Hz, 1H), 3.36 (d, J= 5.9 Hz, 1H), 3.27 - 3.08 (m, 3H), 2.90 - 2.73 (m, 1H), 2.69 - 2.55 (m, 1H), 2.35 (t, J= 8.3 Hz, 1H), 1.82 - 1.64 (m, 1H), 1.38 (t, J= 7.2 Hz, 3H).

[0494] Preparation of Compound 21

[0495] Compound 21 was prepared analogously to 20 (14 mg, 35%) as a white solid. [M+H]+(ESI):318.10.1HNMR (400 MHz, methanol-A) 5 6.98 (s, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 3.75 - 3.61 (m, 2H), 3.34 (d, J = 5.9 Hz, 1H), 3.18-3.10 (m, 1H), 2.89-2.79 (m, 1H), 2.61 (dd, J = 17.5, 10.0 Hz, 1H), 2.39-2.31 (m, 1H), 1.81 - 1.66 (m, 1H), 1.41-1.39 (m, 6H).

[0496] Preparation of Compound 22

[0497] Compound 22 was prepared analogously to 21 and exhibited identical spectral properties to 21.

[0498] Preparation of Compound 24PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0499] STEP 1

[0500] To a mixture of AgF (920 mg, 7.25 mmol) in DMF (50 mL) was added TMSCF3 (1.34 g, 9.43 mmol) under nitrogen at 20°C. and the mixture was stirred at 20°C. for 2 hours. To the mixture was added copper (737 mg, 11.6 mmol), and stirred at 20°C overnight. CuCEi was obtained as a solution in DMF (0.145 M, 50 mL), which was used next step directly. A mixture of the Boc protected amine (80 mg, 0.169 mmol) in CuCEi in DMF (12 mL, 1.69 mmol) was stirred at 20°C for 2 h and 90°C for 10 h under nitrogen. The resulting mixture was filtered and the filter cake was washed with methanol (2 x 20 mL). The filtrate was concentrated under reduced pressure to afford the trifluoromethyl product (80 mg, crude) as a green oil.

[0501] STEP 2

[0502] A solution of of the product from step 1 (50 mg, 0.120 mmol) and HC1 in 1,4-dioxane (4 M) (3 mL) and methanol (3 mL) was stirred at RT for 2 h. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep Cl 8 OBD, 30*150mm, 5um; Mobile Phase A: water / 0.1%FA, Mobile Phase B: acetonitrile; Flow rate: 60 ml / min; Gradient (B%): 9% B to 30% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 7.17) to afford 24 (15 mg, 35%) as an off-white solid. [M+H]+(ESI):316.0. 'H NMR (400 MHz, MeOD) 5 8.72 (s, 1H), 6.97 (s, 1H), 3.86 (s, 3H), 3.76 (s, 3H), 3.69 - 3.54 (m, 1H), 3.42 - 3.31 (m, 1H), 3.16 - 3.05 (m, 1H), 2.93 - 2.76 (m, 2H), 2.71 - 2.57 (m, 1H), 2.45 - 2.37 (m, 1H), 1.83 - 1.65 (m, 1H), 0.99 - 0.86 (m, 4H).

[0503] Preparation of Compound 23

[0504] Compound 23 was prepared analogously to 24 and exhibited identical spectral properties to compound 24.

[0505] Preaparation of Compound 25PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0506] STEP 1

[0507] The Boc iodo starting material (500 mg, 1.15 mmol) was dissolved in HCl / di oxane (5 mL) and the mixture was stirred at RT for 2 h, The residue was concentrated under reduced vacuum to afford the amine product (500 mg, 100%) as a white solid. [M+H]+(ESI):334.00

[0508] STEP 2

[0509] To a solution of the amine from step 1 (500 mg, 1.35 mmol) in toluene (5 mL) was added phthalic anhydride (240 mg, 1.62 mmol) and EtiN (410 mg, 4.06 mmol). The mixture was stirred at 110°C overnight. The reaction was quenched with water and extracted with EtOAc (10 mL x 2). The combined organic layers were concentrated in vacuum to give a residue which was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in water (10 mmol / L NH4HCO3), 40% to 80% gradient in 10 min; detector, UV 220 nm to afford the phthalimide predict (400 mg, 63%) as a white solid. [M+Na]+(ESI):486.05

[0510] STEP 3

[0511] To a solution of the phthalimide product from step 2 (400 mg, 0.86 mmol) in NMP (4 mL) was added methyl 2,2-difluoro-2-sulfoacetate (1.66 g, 8.63 mmol) and Cui (329 mg, 1.72 mmol). The mixture was stirred at 120 °C overnight. After filtration, the residue was purifiedPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in water (10 mmol / L NH4HCO3), 40% to 80% gradient in 10 min; detector, UV 220 nm to afford the trifluoromethyl produc (250 mg, 71%) as a white solid. [M+Na]+(ESI):428.05

[0512] STEP 4

[0513] To a solution of the product from step 3 (250 mg, 0.62 mmol) in EtOH (5 mL) was added hydrazine hydrate (309 mg, 6.16 mmol). The resulting mixture was stirred for 2 h at 80 °C. After cooling to RT the reaction mixture was filtered. The residue was purified by reversed- phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, MeCN in water (10 mmol / L NH4HCO3), 40% to 80% gradient in 10 min; detector, UV 220 nm to afford the deprotected amine (130 mg, 76%) as a yellow oil. [M+H]+(ESI):276.05.

[0514] STEP 5

[0515] To a solution of the product from step 4 (100 mg, 0.36 mmol) in MeCN (2 mL) was added l-fluoro-2-iodoethane (253 mg, 1.45 mmol) and DIEA (235 mg, 1.81 mmol) and the mixture was stirred at 70°C for 12 h. After concentration, the residue was purified by Prep- HPLC (Column: Xselect CSHPrep Cl 8 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% HC1), Mobile Phase B: MeCN; Flow rate: 60 mL / min; Gradient (B%)7-22; Wave Length: 254nm / 220nm; RTl(min): 10.33) to afford 25 (26 mg, 19%) as a white solid. [M+H]+(ESI):322.05. 'H NMR (300 MHz, CD3OD) 5 6.99 (s, 1H), 4.95-4.85 (m, 1H), 4.77-4.68 (m, 1H), 3.85 (s, 3H), 3.79 (s, 3H), 3.65-3.50 (m, 3H), 3.50-3.40 (m, 1H), 3.14-3.02 (m, 1H), 2.88- 2.64 (m, 2H), 2.46-2.34 (m, 1H), 1.94-1.76 (m, 1H).

[0516] Preparation of Compound 26

[0517] Compound 26 was prepared analogously to 25 (13 mg, 19%) and exhibited identical spectral properties to compound 25.

[0518] Preparation of Compound 27

[0519] Compound 27 was prepared from 9 via chiral-SCFchromatograhy and exhibired identical spectral properties to 9.

[0520] Preparation of Compound 28

[0521] Compound 28 was prepared from 9 via chiral-SCFchromatograhy and exhibired identical spectral properties to 9.

[0522] Preparation of Compound 29PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0523] A solution of 4 (100 mg, 0.300 mmol) in toluene : water=10: 1 (2 mL) was treated with methylboronic acid (36 mg, 0.600 mmol) tricyclohexylphosphine (84 mg, 0.300 mmol) and potassium phosphate (97%) (231 mg, 1.050 mmol) and Pd(OAc)2 (13 mg, 0.060 mmol) at 80°C for 3 h under. The crude product was purified by Prep-HPLC with the following conditions [Column: XSelect CSH Prep C18 OBD Column, 19*250 mm, 5pm; Mobile Phase A: water (0.05% HC1), Mobile Phase B: MeCN; Flow rate: 20 mL / min; Gradient: 5% B to 25% B in 9 min; Wave Length: 254nm / 220nm; RTl(min): 6.52] to afford 20 (5 mg, 6%yield) as a white solid. MS m / z [M+H] + (ESI): 222.15. ‘H NMR (300 MHz, Methanol-6 / 4) 3 6.53 (s, 1H), 3.68 (s, 3H), 3.57 (s, 3H), 3.39 (s, 1H), 3.08 (dd, J= 16.6, 4.4 Hz, 1H), 2.95 (d, J= 17.4 Hz, 1H), 2.65 (d, J= 18.7 Hz, 1H), 2.42 (dd, J= 16.8, 9.1 Hz, 1H), 2.16 (s, 4H), 1.68 (s, 1H).

[0524] Preparation of Compound 30

[0525] Compound 30 was prepared analogously to 29 and exhibited identical spectral characteristics as 29.

[0526] Preparation of Compound 32

[0527] A solution of the mixture of iodo isomers (prepared via method published in US 2023 / 0202965 Al by Tanweer Khan et. al), 189 (100 mg, 0.300 mmol) and ethyl-boronic acid (55 mg, 0.750 mmol) and Pd(dppf)C12 (43.92 mg, 0.060 mmol) and potassium phosphate (97%) (198 mg, 0.900 mmol) toluene (2 mL) was stirred at 85°C for 16h under nitrogen The crude product was purified by Prep-Achiral-HPLC with the following conditions [Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% HCL), Mobile Phase B: MeCN; Flow rate: 60 mL / min; Gradient: 3% B to 20% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.52] to afford 32 (2 mg, 3% yield) as a white solid. MS m / z [M+H]+(ESI):236.20. 'H NMR (400 MHz, Methanol-d4) 3 6.54 (s, 1H), 3.69 (s, 3H), 3.57 (s, 3H), 3.43-3.32 (m, 1H), 3.07 (dd, J = 16.9, 5.6 Hz, 1H), 2.94 (dt, J = 17.5, 4.6 Hz, 1H), 2.67 (ddd, JPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699= 17.3, 10.9, 5.6 Hz, 1H), 2.58-2.51 (m, 2H), 2.47-2.39 (m, 1H), 2.09 (dd, J = 11.1, 5.9 Hz,1H), 1.72-1.57 (m, 1H), 1.11 (t, J = 7.6 Hz, 3H).

[0528] Preparation of Compound 33

[0529] STEP 1

[0530] To a mixture of protected amine (280 mg, 0.604 mmol) and 4,4,5,5-tetramethyl-2- (prop-l-en-2-yl)-l,3,2-dioxaborolane (253 mg, 1.510 mmol, 2.5 equiv) in 1,4-dioxane (8 mL) , H2O (2 mL) was added K2CO3 (250 mg, 1.812 mmol) and Pd(dppf)C12CH2C12 (49 mg, 0.060 mmol, 0.1 equiv) at RT under argon. The resulting mixture was stirred at 70°C for additional 16 h. The resulting mixture was diluted with water (lOmL) and extracted with CH2CI2 (3 x 40mL). The combined organic layers were washed with brine (3 x 20 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by Prep-TLC (PE / EA 3 : 1) to afford the product (140 mg, 61% yield) as an off-white solid. [M+H]+(ESI):378.16.

[0531] STEP 2

[0532] To a solution of the product from step 1 (140 mg, 0.371 mmol) in 25 mL THF was added Pd / C (10%, 0.14 g) under nitrogen in alOO mL round-bottom flask. The mixture was hydrogenated at RT for 2 h under hydrogen using a hydrogen balloon, filtered through a Celite pad and concentrated under reduced pressure. The crude product mixture was used in the next step directly without further purification (110 mg, 78%) as an off-white solid. MS m / z [M+H]+(ESI):381.05

[0533] STEP 3PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0534] A solution of the product from step 2 (100 mg, 0.264 mmol) and hydrazine (4 mL) in EtOH (8 mL) was stirred at RT overnight. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: MECN; Flow rate: 60 mL / min; Gradient: 8% B to 25% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.10) to afford 6-isopropyl-5,8- dimethoxy-l,2,3,4-tetrahydronaphthalen-2-amine 33, a mixture of 4 compounds (2 mg, 8% yield, 98.6%) as a white solid. MS m / z [M+H]+(£81) 50.05.^ NMR (300 MHz, Methanol- tZ4) 5 6.68 (s, 1H), 3.80 (d, J = 2.6 Hz, 3H), 3.67 (d, J = 3.1 Hz, 3H), 3.45 (s, 1H), 3.23 -2.42 (m, 5H), 2.17 (s, 1H), 1.83-1.66 (m, 1H), 1.34-1.12 (m, 6H).

[0535] Preparation of Compound 34

[0536] A solution of 5 (180 mg, 0.487 mmol), K3PO4 (620 mg, 2.922 mmol), Pd(dppf)C12- DCM (80 mg, 0.097 mmol), EtsN (49.28 mg, 0.487 mmol) and potassium cyclopropyltrifluoroboranuide (144.12 mg, 0.974 mmol) in toluene (3 mL) was stirred at 110°C overnight under nitrogen. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 220 nm to afford 34 (60 mg, 50%) as a brown solid. [M+H]+(ESI):248.15

[0537] XH NMR (400 MHz, methanol-6 / 4) 5 8.55 (s, 1H), 6.23 (s, 1H), 3.75 (s, 6H), 3.51-3.41 (m, 1H), 3.19-3.01 (m, 2H), 2.83-2.71 (m, 1H), 2.49 (dd, J= 16.9, 9.8 Hz, 1H), 2.24-2.12 (m, 2H), 1.81-1.67 (m, 1H), 1.00-0.94 (m, 2H), 0.73-0.65 (m, 2H).

[0538] Preparation of Compound 35

[0539] Compound 35 was prepared analogously to 34 and exhibited identical spectral characteristics as 34.

[0540] Preparation of Compound 39PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0541] A solution of 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-one (50 mg, 0.242 mmol) in DCM (1 mL) was treated with isobutylamine (21 mg, 0.290 mmol) at 0°C for 30min followed by the addition of sodium cyanoboranuide (46 mg, 0.726 mmol) in portions at 0°C.The mixture was heated to 0 °C for Ih. The resulting mixture was extracted with DCM (3 x 5mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was purified by Prep-HPLC with the following conditions: Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% HCL), Mobile Phase B: MeCN; Flow rate: 60 mL / min; Gradient: 9% B to 12% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 10.08 to afford 39 (3 mg) as a white solid. [M+H]+(ESI):264. 'H NMR (300 MHz, Methanol-d4) 5 6.75 (s, 2H), 3.77 (d, J = 5.4 Hz, 6H), 3.47- 3.35 (m, 2H), 3.08-2.97 (m, 3H), 2.66-2.50 (m, 2H), 2.34-2.30 (m, IH), 2.11-1.98 (m, IH), 1.79-1.66 (m, IH), 1.08 (d, J= 6.6 Hz, 6H).

[0542] Preparation of Compound 404§

[0543] To a stirred solution of 4 (20 mg, 0.060 mmol) and acetaldehyde (3 mg, 0.066 mmol in methanol (0.5 mL) were added HOAc (0.4 mg, 0.006 mmol) and sodium cyanoborohydride (6 mg, 0.090 mmol) in portions a tO °C under nitrogen. The resulting mixture was stirred at RT for 5h. The reaction was quenched by the addition of sat. sodium hyposulfite (aq.) (2mL) at RT. The resulting mixture was extracted with ethyl acetate (3 x lOmL). The combined organic layers were washed with brine (3x5 mL) and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, MeCN in water (0.1% HC1), 10% to 50% gradient in 10 min; detector, UV 220 nm which afforded 40 (7 mg, 28%) as a light yellow solid. [M+H]+(ESI):361.95. 'H NMR (500 MHz, Methanol-A) 5 7.20 (s, IH), 3.82 (s, 3H), 3.74 (s, 3H), 3.55-3.45 (m, IH), 3.28-PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26993.18 (m, 3H), 3.17-3.09 (m, 1H), 2.88-2.79 (m, 1H), 2.57-2.48 (m, 1H), 2.36-2.27 (m, 1H), 1.81-1.69 (m, 1H), 1.42-1.34 (m, 3H).

[0544] Preparation of Compound 41

[0545] Compound 41 was prepared analogously to 40 and exhibited identical spectral properties to compound 40

[0546] Preapration of Compound 42

[0547] Compound 42 was prepared analogously to 40, (2 mg, 8.59%) as a light yellow solid. [M+H]+(ESI):362.05. 'H NMR (500 MHz, Methanol-A) 5 8.56 (s, 1H), 7.18 (s, 1H), 3.80 (s, 3H), 3.75 (s, 3H), 3.48-3.37 (m, 2H), 3.25-3.14 (m, 2H), 2.99-2.90 (m, 1H), 2.78-2.70 (m, 1H), 2.69-2.57 (m, 1H), 2.36-2.27 (m, 1H), 1.82-1.71 (m, 1H), 1.41-1.31 (m, 3H).

[0548] Preparation of Comound 43

[0549] Compound 43 was prepared analogously to 40 and exhibited identical spectral properties to compound 42

[0550] Preapration of Compound 44

[0551] Compound 44 was prepared analoguesly to 39, 0 (19 mg) as a white solid. LCMS [M+H]+ (ESI): 290. ‘HNMR (300 MHz, Methanol-d4) 56.76 (s, 2H), 4.25-4.15 (m, 2H), 3.79 (s, 3H), 3.77 (s, 3H), 3.65-3.53 (m, 1H), 3.40-3.33 (m, 1H), 3.11-3.02 (m, lH).2.68-2.55 (m, 2H), 2.42-2.33 (m, 1H), 1.83-1.69 (m, 1H).

[0552] Preparation of Compound 45PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0553] STEP 1

[0554] A mixture of the boc iodo starting material (100 mg, 0.23 mmol) and NaH (8 mg, 0.35 mmol) in THF (1 mL) was stirred at 0°C for 30 min under nitrogen. To the above mixture, iodoethane (43 mg, 0.28 mmol) was added at 0°C under nitrogen. The resulting mixture was stirred at RT for 1 h under nitrogen. The reaction was quenched with water at 0°C. The resulting mixture was extracted with DCM (3 x 40 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed- phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 50% to 100% gradient in 10 min; detector, UV 220 nm to afford the ethylated productin (60 mg, 56%) as an off-white oil. [M+H]+(ESI):462.00. ‘H NMR (300 MHz, methanol-d4) 5 7.21 (s, 1H), 4.11 (s, 1H), 3.87 (d, J = 1.2 Hz, 6H), 3.21 (s, 6H), 3.12 (s, 1H), 2.96 (dd, J = 17.6, 5.9 Hz, 1H), 2.76 - 2.60 (m, 1H), 2.00 (s, 1H), 1.96 - 1.82 (m, 1H), 1.48 (s, 9H), 1.19 (t, J = 7.0 Hz, 3H).

[0555] STEP 2

[0556] A mixture of the product from step 1 (25 mg, 0.054 mmol), sodium methanesulfmate (27 mg, 0.270 mmol), Cui (1 mg, 0.005 mmol), K3PO4 (34 mg, 0.16 mmol) and (2S)- pyrrolidine-2-carboxylic acid (1.25 mg, 0.011 mmol) in DMSO (1 mL) was stirred at 115°C overnight under nitrogen. The resulting mixture was diluted with water (5 mL) and extractedPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 with ethyl acetate (3 x 5 mL). The combined organic layers were washed with saturated NaCl (10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (10 mmol / L NH4HCO3 +0.05% NH3.H2O), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient: 49% B to 70% B in 10 min; Wave Length: 254nm / 220nm; RTl(min): 7.42) to afford the methyl sulfone product (4 mg, 16%) as a white solid. [M+H]+(ESI):414.05.

[0557] STEP 3

[0558] To a stirred solution of the product from step 2 (20 mg, 0.048 mmol, 1 equiv.) in 1,4- dioxane (0.5 mL) was added HC1 in 1,4-dioxane (4.0 M) (0.5 mL) dropwise at room temperature. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: XBridge Shield RP18 OBD Columnl9*250 mm, 5pm; Mobile Phase A: water (0.05% HC1), Mobile Phase B: acetonitrile; Flow rate: 20mL / min; Gradient: 2% B to 12% B in 10 min; Wave Length: 254nm / 220nm; RTl(min): 7.82 / 9.35) to afford 45 (3 mg, 19%) as a white solid. [M+H]+(ESI):314.05. 'HNMR (300 MHz, methanol-d4) 5 7.28 (s, 1H), 3.89 (d, J= 4.7 Hz, 6H), 3.55 (s, 1H), 3.38 (d, J= 5.7 Hz, 1H), 3.30 - 3.09 (m, 6H), 2.86 (tt, 7= 11.5, 5.3 Hz, 1H), 2.63 (dd, J= 17.6, 9.8 Hz, 1H), 2.36 (d, J= 9.3 Hz, 1H), 1.79 -1.74 (m, 1H), 1.37 (t, J= 7.3 Hz, 3H).

[0559] Preparation of Compound 46

[0560] Compound 46 was prepared analogously to 45 starting with the opposite enantiomer and exhibited identical spectral properties to 45.

[0561] Preparation of Compounnd 47

[0562] STEP 1

[0563] A mixture of of the product from step 1 of the preparation of 45 (60 mg, 0.130 mmol), Cui (2 mg, 0.013 mmol) and zinc acetate, anhydrous (42 mg, 0.195 mmol) in DMSO (1 mL) was stirred at 135°C overnight under nitrogen. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 0% to 100% gradient in 10 min; detector, UV 220 to afford the crude product which was used as is in the next step.

[0564] STEP 2

[0565] A mixture of the product from step 1 (30 mg, 0.079 mmol), (acetyloxy)(phenyl)-lA[3]- iodanyl acetate (63 mg, 0.198 mmol) and ammonium carbamate (12 mg, 0.158 mmol) in methanol (1 mL) was stirred at RT for 3 h . The reaction was quenched with saturated NH4CI (aq.) (1 mL). The resulting mixture was extracted with ethyl acetate (2 x 10 mL). The combinedPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 organic layers were washed with saturated NaCl (10 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The crude product (30 mg) which was used in the next step directly without further purification. [M+H]+(ESI):413.15.

[0566] STEP 3

[0567] To a stirred solution of the product from step 3(30 mg, 0.073 mmol, 1) in DCM (1 mL) was added trifluoroacetic acid (0.2 mL) dropwise at RT. Then the mixture was stirred at 25°C for 1 h. After concentration, the crude material was purified by Prep-HPLC (Column: XBridge Shield RP18 OBD Columnl9*250 mm, 5pm; Mobile Phase A: water (0.05% HC1), Mobile Phase B: acetonitrile; Flow rate: 20mL / min; Gradient: 2% B to 12% B in 10 min; Wave Length: 254nm / 220nm; RTl(min): 7.82 / 9.35.) which afforded 47 (14 mg, 60%) as a yellow solid. [M+H-100]+(ESI):313.05 .'HNMR (400 MHz, methanol-^) 5 7.32 (d, J= 9.9 Hz, 1H), 4.01- 3.93 (m, 6H), 3.90 (d, J= 9.2 Hz, 3H), 3.63 (d, J= 8.3 Hz, 1H), 3.39 (dd, J= 15.7, 8.8 Hz, 1H), 3.25-3.12 (m, 3H), 2.93 (d, J= 16.3 Hz, 1H), 2.74-2.71 (m, 1H), 2.50 - 2.31 (m, 1H), 1.93- 1.63 (m, 1H), 1.39 (t, J= 7.0 Hz, 3H).

[0568] Preparation of Compound 48

[0569] Compound 48 was prepared analogously to 47 starting with the opposite enantiomer and exhibited identical spectral properties to 47.

[0570] Preparation of Compound 49

[0571] A solution of single enantiomer of 9 (70 mg, 0.24 mmol), DIEA (158 mg, 1.22 mmol) and 2-iodopropane (417 mg, 2.45 mmol) in MeCN (1 mL) was stirred at 80°C overnight. After concentration, the crude product was purified by Prep-HPLC with the following conditions (Column: XBridge C18 OBD Column, 19*250 mm, 5pm; Mobile Phase A: water (0.05% HC1), Mobile Phase B: MeOH; Flow rate: 25 mL / min; Gradient (B%): 12% B to 45% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 7.5) to afford 49 (26 mg, 29%) as an off-white solid. [M+H]+(ESI):328.10. ‘HNMR (400 MHz, CD3OD) 5 7.27 (s, 1H), 3.89 (s, 3H), 3.88 (s, 3H), 3.76-3.61 (m, 2H), 3.40-3.31 (m, 1H), 3.22-3.13 (m, 4H), 2.95-2.82 (m, 1H), 2.67-2.56 (m, 1H), 2.41-2.31 (m, 1H), 1.80-1.66 (m, 1H), 1.34 (d, J= 6.8 Hz, 6H).

[0572] Preparation of Compound 50PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0573] Compound 50 was prepared analogously to 49 from the opposite enantiomer and exhibited identical spectral characteristics to 49.

[0574] Preparation of Compound 51

[0575] Compound 51 was prepared analogously to 90,(29 mg, 35%) as a white solid. [M+H]+(ESI):250.15. 'H NMR (300 MHz, CD3OD) 5 6.67 (s, 1H), 3.80 (s, 3H), 3.67 (s, 3H), 3.47 (t, J= 10.0 Hz, 1H), 3.23 -2.97 (m, 3H), 2.85-2.71 (m, 1H), 2.51 (dd, J= 16.9, 9.7 Hz, 1H), 2.18 (s, 1H), 1.84-1.65 (m, 1H), 1.22 (d, J= 6.7 Hz, 6H).

[0576] Preparatiom of Compound 52

[0577] Compound 52 was prepated analogously55 to 51and exhibited identical spectral properties.

[0578] Preparation of Compound 54

[0579] To a stirred solution of 4 (20 mg, 0.060 mmol) and 37% formaldehyde solution (20 uL, 0.67 mmol) in methanol (0.1 mL) were added acetic acid (0.01 mL, 0.012 mmol) and sodium cyanoborohydride (11.32 mg, 0.180 mmol, 3 ) dropwise at 0°C under nitrogen atmosphere. The resulting mixture was stirred at RT for 2 h under nitrogen atmosphere. The resulting mixture was extracted with ethyl acetate (3 x 5 mL). The combined organic layers were washed with saturated NaCl (2 x 5 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep- HPLC with the following conditions [Column: Xselect CSH Prep Cl 8 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient: 5% B to 25% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.41] to afford 54 (6.0 mg, 25%) as an off-white solid. [M+H]+(ESI):362.00.1H NMR (300 MHz, methanol- tZ4) 5 7.20 (s, 1H), 3.83 (s, 3H), 3.73 (s, 3H), 3.68-3.55 (m, 1H), 3.28-3.16 (m, 2H), 2.98 (s, 6H), 2.91-2.79 (m, 1H), 2.78-2.63 (m, 1H), 2.42-2.29 (m, 1H), 1.89-1.73 (m, 1H).

[0580] Preparation of Compound 53

[0581] Compound 53 was prepared analogously to 54 exhibited identical spectral properties to 70.

[0582] Praparation of Compound 55PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0583] To a stirred solution of 40 (25 mg, 0.075 mmol) and acetaldehyde (8 mg, 0.188 mmol) in methanol (0.5 mL) were added sodium cyanoborohydride (7.07 mg, 0.112 mmol, 1.5 equiv.) and acetic acid (6 mg, 0.112 mmol) dropwise / in portions at 0°C under nitrogen. The resulting mixture was stirred at RT for 2 h. The reaction was quenched by the addition of sat. sodium hyposulfite (aq.) (5mL) at RT. The resulting mixture was extracted with dichloromethane (15 mL). The organic layer was washed with brine (3x5 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-Achiral-HPLC with the following conditions [Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% HCL), Mobile Phase B: MECN; Flow rate: 60 mL / min; Gradient: 5% B to 25% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.41] to afford 55 (5 mg, 16%) as a white solid. [M+H]+(ESI):390.00. 'H NMR (300 MHz, Methanol-A) 5 7.17 (s, 1H), 3.80 (s, 3H), 3.71 (s, 4H), 3.50-3.33 (m, 3H), 3.28- 2.99 (m, 3H), 2.89-2.65 (m, 2H), 2.39-2.25 (m, 1H), 1.94-1.75 (m, 1H), 1.46-1.34 (m, 6H).

[0584] Preparation of Compound 56

[0585] A solution of 5 (30 mg, 0.081 mmol), DIEA (31 mg, 0.24 mmol) and 2-iodopropane (41 mg, 0.24 mmol) in acetonitrile (0.5 mL) was stirred at 100°C overnight under nitrogen. After concentration in vacuo, the crude product was purified by Prep-HPLC with the following conditions (Column: F-phenyl Prep OBD C18 Column, 30*150 mm, 5pm; Mobile Phase A: water (0.1% HC1), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): isocratic 3-20; Wave Length: 254nm / 220nm; RTl(min): 9.23) to afford 56 (12 mg, 56%) as a yellow solid. [M+H]+(ESI):376.0. ‘H NMR (300 MHz, methanol-A) 5 7.17 (s, 1H), 3.80 (s, 3H), 3.72 (s, 3H), 3.72 - 3.55 (m, 2H), 3.30 -2.83 (m, 3H), 2.56 - 2.41 (m, 1H), 2.32 - 2.21(m, 1H), 1.82 - 1.63 (m, 1H), 1.43 - 1.34 (m, 6H).

[0586] Preparation of Compound 57PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0587] Compound 57 was prepared analogously to 56 starting with compound 4 and exhibited identical spectral properties to 56.

[0588] Preparation of Compound 58

[0589] Compound 58 was prepared analogously to 56 . [M+H]+(ESI):376.00.1H NMR (300 MHz, methanol-A) 5 7.17 (s, 1H), 3.76 (d, J= 12.3 Hz, 6H), 3.65 -3.61 (m, J= 11.7, 6.0 Hz, 2H), 3.58 (s, 1H), 2.99 - 2.93 (m, 1H), 2.69-2.62 (m, 2H), 2.37 - 2.24 (m, 1H), 1.73-1.65 (m, 1H), 1.38 (d, 7= 6.5 Hz, 6H).

[0590] Preparation of Compound 59

[0591] Preparation of Compound 57

[0592] Compound 57 was prepared analogously to 56 starting with compound 4 and exhibited identical spectral properties to 56.

[0593] Preparation of Compound 58

[0594]

[0595] Compound 58 was prepared analogously to 56 . [M+H]+(ESI):376.00.1H NMR (300 MHz, methanol-t / 4) 5 7.17 (s, 1H), 3.76 (d, J= 12.3 Hz, 6H), 3.65 -3.61 (m, J= 11.7, 6.0 Hz, 2H), 3.58 (s, 1H), 2.99 - 2.93 (m, 1H), 2.69-2.62 (m, 2H), 2.37 - 2.24 (m, 1H), 1.73-1.65 (m, 1H), 1.38 (d, 7= 6.5 Hz, 6H).

[0596] Preparation of Compound 59

[0597] STEP 1

[0598] A mixture of 1 (425 mg, 1.48 mmol) and NBS (288 mg, 1.62 mmol) in DCM (4 mL) was stirred at RT overnight. The reaction was quenched with water. The mixture was basified to pH 10 with saturated Na2COs (aq.). The resulting mixture was extracted with Ethyl acetate (3 x 30 mL). The combined organic layers were washed with saturated NaCl (2 x 10 mL), driedPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in Water (0.1% TFA), 10% to 100% gradient in 10 min; detector, UV 220 nm to afford the bromo product as mixture of isomers (350 mg, 82%) as a yellow solid. [M+H]+(ESI):286.05.

[0599] STEP 2

[0600] The isomers from step 1 (300 mg, 1.05 mmol) were separated by Prep-chiral-HPLC with follow conditions (Column: CHIRALPAK IC, 2*25 cm, 5 pm; Mobile Phase A: HEX (0.5% 2 M NHs-methanol), Mobile Phase B: EtOH: DCM=1 : 1; Flow rate: 20 mL / min; Gradient (B%): isocratic 7; Wave Length: 220 / 254 nm; RTl(min): 16.448; RT2(min): 19.283; Sample Solvent: EtOH; Injection Volume: 0.5 mL; Number of Runs: 23). This afforded in the single isomer (80 mg, 28%) as a white solid. [M+H]+(ESI):286.05.

[0601] STEP 3

[0602] A mixture of pure isomer from step 2 (30 mg, 0.105 mmol), acetaldehyde (12 mg, 0.105 mmol), sodium cyanoborohydride (14 mg, 0.21 mmol) and acetic acid (6 mg, 0.105 mmol) in methanol (2 mL) was stirred at RT for 1 h. After concentration, the crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% HC1), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 9% B to 22% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.88) to afford 59 (22 mg) as a white solid. [M+H]+(ESI):314.00.JH NMR (300 MHz, methanol-A) 5 7.00 (s, 1H), 3.81 (s, 3H), 3.75 (s, 3H), 3.49 (d, J= 7.3 Hz, 1H), 3.26 - 3.03 (m, 4H), 2.80 (ddd, 7 = 17.5, 11.3, 5.5 Hz, 1H), 2.51 (dd, J= 16.7, 10.0 Hz, 1H), 2.37 - 2.23 (m, 1H), 1.84 - 1.64 (m, 1H), 1.36 (t, J= 7.3 Hz, 3H).

[0603] Preparation of Compound 60

[0604] Compound 60 was prepared analogously to 59 starting with the other bromo isomer from the chromatographic separation (11 mg, 30%) as a white solid. [M+H]+(ESI):314.00. 'H NMR (300 MHz, methanol-A) 5 7.00 (s, 1H), 3.78 (d, J= 6.1 Hz, 6H), 3.45 (s, 1H), 3.20 - 3.14 (m, 2H), 3.00 - 2.86 (m, 1H), 2.79 - 2.51 (m, 1H), 2.31 (s, 1H), 1.83 - 1.68 (m, 1H), 1.41 - 1.26 (m, 3H).

[0605] Praparation of Compound 61

[0606] Compound 61 was prepared analogously to 60 and exhibited identical spectral properties to 60.

[0607] Preparation of Compound 62PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0608] Compound 62 was prepared analogously to 61 starting with it is enanatiomer and exhibited identical spectral properties to 61.

[0609] Preparation of Compound 63

[0610] Compound 63 was prepared analogously to 59 starting with it is enanatiomer and exhibited identical spectral properties to 59.

[0611] Preparation of Compound 64

[0612] Compound 64 was prepared analogously to 59 via chlorination with NCS instead of NBS, (26 mg, 50%) as a white solid. [M+H]+(ESI): 270. 'HNMR (300 MHz, methanol-^) 5 6.87 (s, 1H), 3.78 (d, J= 15.3 Hz, 6H), 3.57 - 3.40 (m, 1H), 3.25 - 3.03 (m, 4H), 2.86 - 2.70 (m, 1H), 2.52 (dd, J= 16.9, 10.1 Hz, 1H), 2.29 (s, 1H), 1.76 (td, J= 11.4, 5.1 Hz, 1H), 1.36 (t, 7= 7.3 Hz, 3H).

[0613] Preparation of Compound 65

[0614] Compound 65 was prepared analogously to 64 and exhibited identical spectral properties.

[0615] Preparation of Compound 69

[0616] STEP 1

[0617] A mixture of the protected amine (60 mg, 0.180 mmol), l,l,l-trifluoro-2-iodoethane (75 mg, 0.360 mmol), Pd(OAc)2 (4 mg, 0.018 mmol), CS2CO3 (117 mg, 0.360 mmol) and XantPhos (20 mg, 0.036 mmol) in toluene (1.5 mL) was stirred at 30°C for 42 h under nitrogen and under blue LEDs (450 nm). The reaction was quenched with water (10 mL). The resulting mixture was extracted with ethyl acetate (3 x 20 mL). The combined organic layers were washed with saturated NaCl (2 x 10 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase,PCT / US25 / 44749 03 September 2025 (03.09.2025)Attorney Docket No.: ATAI-II5 / 0IWO 338067-2699 acetonitrile in water (10 mmol / L NH4HCO3), 10% to 100% gradient in 10 min; detector, UV 220 nm which afforded the product (10 mg, 13%) as a colorless oil. [M+H-100]+(ESI):316.05.

[0618] STEP 2

[0619] A mixture of the product from step 1 (10 mg, 0.024 mmol) and 10% Pd / C (5 mg) in methanol (1 mL) was stirred at RT for 1 h under hydrogen (5 atm.). The resulting mixture was filtered and the filter cake was washed with methanol (2 x 5 mL). The filtrate was concentrated under reduced pressure to afford the product (10 mg, crude) was used in the next step directly without further purification.

[0620] STEP 3

[0621] A mixture of the product from step 2 (6 mg, 0.014 mmol) in HC1 in 1,4-dioxane (4.0 M) (1 mL) was stirred at RT for 1 h. After concentration, the crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep Cl 8 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% HC1), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 14% B to 30% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 7.32) to afford 69 (1.2 mg, 23%) as a white solid. [M+H]+(ESI): 318.15.XH NMR (300 MHz, methanol- tZ4) 5 6.65 (s, 1H), 3.80 (s, 3H), 3.68 (s, 3H), 3.34 (s, 2H), 3.15 (d, J= 5.4 Hz, 3H), 2.79 (s, 1H), 2.75-2.64 (m, 2H), 2.52 - 2.49 (m, 1H), 2.23 - 2.08 (m, 2H), 1.92 - 1.75 (m, 2H).

[0622] Preparation of 7171

[0623] STEP 1

[0624] A mixture of the Boc protected amine (50 mg, 0.115 mmol), but-l-yn-1- yltrimethylsilane (43 mg, 0.345 mmol), EtiN (35 mg, 0.345 mmol), Cui (5 mg, 0.023 mmol), Pd(OAc)2 (8 mg, 0.035 mmol), dppf (38 mg, 0.069 mmol) and tetra-n-butylammonium fluoride (1.0M in THF) (0.35 mL, 0.345 mmol) in DMSO (1 mL) was stirred at 50°C overnight underPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 nitrogen. The resulting mixture was diluted with water (5 mL) and then extracted with Ethyl acetate (3 x 10 mL). The combined organic layers were washed with saturated NaCl (2 x 10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 50% to 100% gradient in 10 min; detector, UV 220 nm which afforded the product (40 mg, 96%) as a brown yellow oil. [M+H-100]+(ESI):260.15.

[0625] STEP 2

[0626] A mixture of the product from step 1(40 mg, 0.111 mmol and 10% Pd / C (20 mg) in methanol (1 mL) was stirred at RT overnight under hydrogen (5 atm). The resulting mixture was filtered and the filter cake was washed with methanol (2 x 10 mL). The filtrate was concentrated under reduced pressure to provide the product (40 mg, crude) was used in the next step directly without further purification. [M+H-56]+(ESI):308.05.

[0627] STEP 3

[0628] A mixture of the product from step 2 (30 mg, 0.083 mmol) and HC1 in 1,4-dioxane (4.0 M) (0.5 mL, 2.00 mmol) in dioxane (1 mL) was stirred at RT for 1 h. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep Cl 8 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 14% B to 30% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.12) to afford 71 (5 mg, 19% yield, 98%) as a white solid. [M+H-100]+(ESI):264.15.1HNMR (300 MHz, methanol-A) 56.62 (s, 1H), 3.78 (s, 3H), 3.67 (s, 3H), 3.46 (s, 1H), 3.34 (s, 1H), 3.29 - 3.06 (m, 1H), 3.01 (t, J = 4.7 Hz, 1H), 2.77 (ddd, J= 17.0, 10.8, 5.6 Hz, 1H), 2.67 - 2.42 (m, 2H), 2.19 (d, J= 11.9 Hz, 1H), 1.83 - 1.66 (m, 3H), 1.58 -1.53 (m, J= 15.6, 7.6 Hz, 2H), 1.48-1.26 (m, 2H), 0.99 -0.97 (m, J= 22.6, 7.3 Hz, 4H).

[0629] Preaparation of Compound 70

[0630] Compound 70 was prepared analoguesly to 71 and exhibited identical spectral charachteristics.

[0631] Preparation of Compound 72PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0632] STEP 1

[0633] To a stirred mixture of starting alcohol (100 mg, 0.264 mmol) in DCM (2 mL) was added Dess-Martin reagent (224 mg, 0.528 mmol) in portions at 0°C under nitrogen. The resulting mixture was stirred at RT for 3 h. The reaction was poured into ice water (2 mL). The resulting mixture was extracted with DCM (3 x 10 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure to afford the aldehyde (100 mg) which was used in the next step directly without further purification.

[0634] STEP 2

[0635] To a stirred solution of the product from step 1 (90 mg, 0.238 mmol) in DCM (1 mL) was added diethylaminosulfur trifluoride (0.06 mL, 0.476 mmol) dropwise at 0°C. The resulting mixture was stirred at RT for 2 h. The reaction was added into saturated NaHCO3(aq) (5 mL) at 0°C. The resulting mixture was extracted with DCM (3 x 10 mL). The combined organic layers were washed with saturated NaCl (10 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 5% to 100% gradient in 10 min; detector, UV 220 nm to afford the difluoro product (20 mg, 21%) as a colorless oil. [M+H+22]+(ESI):422.15.

[0636] STEP 3

[0637] A mixture of the product from step 2 (20 mg, 0.050 mmol) and HC1 in 1,4-di oxane (4.0 M) (1 mL) in dioxane (1 mL) was stirred at RT for 1 h. The crude product was purified by Prep-HPLC with following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm,PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26995um; Mobile Phase A: water (0.1% HC1), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 10% B to 25% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 10.2) which afforded 72 (9 mg, 54%) as a white solid. [M+H]+(ESI):282.10. 'H NMR (300 MHz, methanol-A) 5 6.65 (s, 1H), 5.88 (t, J= 4.2 Hz, 1H), 3.79 (s, 3H), 3.68 (s, 3H), 3.55 - 3.46 (m, 1H), 3.17 (dd, J= 17.0, 5.8 Hz, 1H), 3.10 - 2.98 (m, 1H), 2.87 - 2.65 (m, 3H), 2.48 (d, = 9.8 Hz, 1H), 2.20 (d, J= 12.6 Hz, 1H), 1.90 - 1.67 (m, 5H)

[0638] Preparation of Compound 73

[0639] Compound 73 was prepared analogously to 72 beginning with the corresponding enantiomer and exhibited identical spectral properties to 72.

[0640] Prearation of Compound 74

[0641] Compound 74 was prepared analogously to 72 but omitting the oxidation step, as a white solid. [M+H]+(ESI):282.15.XH NMR (400 MHz, methanol-A) 5 6.65 (s, 1H), 4.50 (t, J = 5.6 Hz, 1H), 4.38 (t, J= 5.5 Hz, 1H), 3.79 (s, 3H), 3.67 (s, 3H), 3.47 (dd, J = 21.2, 4.3 Hz, 1H), 3.17 (dd, J= 17.3, 6.0 Hz, 1H), 3.05 - 3.02 (m, 1H), 2.80 (dd, J= 11.1, 5.8 Hz, 1H), 2.63 - 2.61 (m, 2H), 2.50 (dd, J= 16.8, 9.7 Hz, 1H), 2.18 (s, 1H), 1.82-1.62 (m,5H).

[0642] Prearation of Compound 75

[0643] Compound 75 was prepared analogously to 74 beginning with the corresponding enantiomer and exhibited identical spectral properties to 74.

[0644] Preparation of Compound 76w

[0645] STEP 1

[0646] A mixture of the iodo starting material (50 mg, 0.115 mmol), cyclopropylboronic acid (19 mg, 0.230 mmol), Pd(dppf)C12-DCM (10 mg, 0.012 mmol) and K2CO3 (47 mg, 0.345 mmol) in dioxane (1 mL) was stirred at 80°C overnight under nitrogen. The reaction was quenched with water (5 mL). The resulting mixture was extracted with ethyl acetate (3 x 10PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 mL). The combined organic layers were washed with saturated NaCl (10 mL), and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 10% to 100% gradient in 10 min; detector, UV 220 nm which afforded the cycloprylated product (15 mg, 37%) as a yellow oil. [M+H-56]+(ESI):292.15.

[0647] STEP 2

[0648] A solution of the product from step 1 (15 mg, 0.043 mmol) in DMF (1 mL) was treated with NaH (5 mg, 0.065 mmol, 60% in mineral oil) at 0°C for 1 h under nitrogen followed by the addition of Mel (9 mg, 0.052 mmol) dropwise. The resulting mixture was stirred at RT for 2 h under. The reaction was quenched with water and the resulting mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with saturated NaCl (2 x 10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 10% to 100% gradient in 10 min; detector, UV 220 nm which afforded the product (8 mg, 51%) as a yellow oil. [M+H-100]+(ESI):262.15.

[0649] STEP 3

[0650] A solution of the product from step 2 (8 mg, 0.022 mmol) and trifluoroacetic acid (8 mg, 0.066 mmol) in DCM (2 mL) was stirred at RT for 1 h The resulting mixture was concentrated under vacuum and the he crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 9% B to 22% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.88) to afford 76 (3.6 mg, 52%) as a white solid. [M+H]+(ESI):262.15.1HNMR (300 MHz, methanol-d4) 5 8.52 (s, 1H), 6.23 (s, 1H), 3.75 (d, J = 2.9 Hz, 6H), 3.46 - 3.31 (m, 2H), 3.25 - 3.00 (m, 2H), 2.86 - 2.67 (m, 4H), 2.52 (dd, J = 16.8, 9.6 Hz, 1H), 2.28 (d, J = 12.8 Hz, 1H), 2.24 - 2.09 (m, 1H), 1.83 - 1.64 (m, 1H), 1.04 - 0.89 (m, 2H), 0.73 - 0.62 (m, 2H).

[0651] Preparation of Compound 77

[0652] Compound 77 was prepared analogously to 76 beginning with the corresponding enantiomer and exhibited identical spectral properties to 76.

[0653] Prepartion of 78

[0654] Compound 78 was prepared analogously to 76 (10 mg, 57% yield) as a white solid. [M+H]+(ESI):276.15. E NMR (300 MHz, methanol-d4) 5 8.54 (s, 1H), 6.23 (s, 1H), 3.75 (d,PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699J = 3.0 Hz, 6H), 3.51 - 3.36 (m, 1H), 3.26 - 3.03 (m, 4H), 2.85 - 2.68 (m, 1H), 2.58 - 2.43 (m, 1H), 2.30 (d, J = 12.4 Hz, 1H), 2.23 - 2.11 (m, 1H), 1.83 - 1.61 (m, 1H), 1.35 (t, J = 7.2 Hz, 3H), 1.04 - 0.92 (m, 2H), 0.71 - 0.62 (m, 2H).

[0655] Preparation of 79

[0656] Compound 79 was prepared analogously to 78 beginning with the corresponding enantiomer and exhibited identical spectral properties to 78.

[0657] Preparation of Compound 80

[0658] STEP 1

[0659] A solution of 4 (180 mg, 0.487 mmol), K3PO4 (620 mg, 2.92 mmol), Pd(dppf)C12-DCM (80 mg, 0.097 mmol), EtsN (49 mg, 0.487 mmol) and potassium cyclopropyltrifluoroboranuide (144 mg, 0.974 mmol) in toluene (3 mL) was stirred at 110°C overnight under nitrogen. The reaction mixture was cooled to RT, the reaction mixture was diluted with water (5 mL) and then extracted with ethyl acetate (5 mL x 3). The combined organic layers were concentrated in vacuum to give a residue which was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 220 nm to afford the product (80 mg, 66%) as a brown solid. [M+H]+(ESI):248.1

[0660] STEP 2

[0661] A solution of of the product from step 1 (20 mg, 0.081 mmol), DIEA (42 uL, 0.243 mmol, 3 equiv.) and 2-iodopropane (137 mg, 0.810 mmol) in acetonitrile (1 mL) was stirred at 80°C overnight under nitrogen. After concentration, the crude product was purified by Prep- HPLC with the following conditions (Column: XSelect CSH Prep Cl 8 OBD Column, 19*250 mm, 5pm; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 20 ml / min; Gradient (B%): 13% B to 30% B in 12 min; Wave Length: 254nm / 220nm; RTl(min): 10.25) to afford 80 (8 mg, 30%) as an off-white solid. [M+H]+(ESI): 290.1. 'H NMR (300 MHz, methanol-A) 5 8.46 (s, 1H), 6.23 (s, 1H), 3.79 - 3.60 (m, 6H), 3.64 - 3.48 (m, 2H), 3.31 - 3.04 (m, 2H), 2.83 - 2.65 (m, 1H), 2.54 - 2.38 (m, 1H), 2.34 - 2.14 (m, 2H), 1.80 - 1.54 (m, 1H), 1.42 - 1.33 (m, 6H), 1.03 - 0.91 (m, 2H), 0.77 - 0.54 (m, 2H).

[0662] Preparation of Compound 81PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0663] Compound 81 was prepared analogously to 80 beginning with the corresponding enantiomer and exhibited identical spectral properties to 80.

[0664] Preparation of Compound 83

[0665] STEP 1

[0666] A solution of 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-one (15 g, 72 mmol), cyclopropanamine (8.31 g, 145 mmol), sodium cyanoborohydride (9.14 g, 145 mmol) and HO Ac (0.44 g, 7.27 mmol) in methanol (150 mL) was stirred at RT for 2 h. The mixture was basified to pH 10 with saturated Na2COs (aq.). The resulting mixture was concentrated under reduced pressure. The resulting mixture was extracted with ethyl acetate (2 x 1 L) and dried over anhydrous Na2SO4. After filtration, the combined sxtracts were concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in Water (10 mmol / LPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 220 nm. to afford 167 (10 g, 52%) as a brown oil.

[0667] STEP 2

[0668] The enantiomers of 167 (10 g) were separated by Prep-Chiral HPLC with the following conditions (Column: CHIRALPAK PAK AD-H, 30*250mm; Mobile Phase A: CO2, Mobile Phase B: IPA (0.1% 7 M NEE-methanol); Flow rate: 100 mL / min; Gradient (B%): isocratic 30% B; RTl(min): 3; RT2(min): 5; Sample Solvent: methanol; Injection Volume: 3 mL; Number of Runs: 30) to afford the pair of enantiomers (3.5 g, 33%) and (3.5 g, 33% yield) as brown oils.

[0669] STEP 3

[0670] A solution of the single enantiomer from step 2 (3 g, 9.1 mmol), I2 (9.28 g, 36 mmol) and Ag2SO4(15.20 g, 37 mmol) in methanol (60 mL) was stirred at RT for 12 h. The resulting mixture was filtered and the filter cake was washed with methanol (10 mL x 4). The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 254 nm to afford the product (1.2 g, 34%) as a brown solid.

[0671] STEP 4

[0672] A solution of the product from step 3 (1.2 g, 3.2 mmol), NaHCCh (539 mg, 6.41 mmol) and BOC2O (840 mg, 3.85 mmol) in THF (5 mL) and H2O (1 mL) was stirred at RT for overnight. After concentration, the residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 50% to 90% gradient in 20 min; detector, UV 220 nm to afford the product (700 mg, 46%) as a brown solid.

[0673] STEP 5

[0674] The iodo isomers from step 4 (700 mg) were separated by Prep-SFC with the following conditions (Column: CHIRALPAK AD-3, 3*100mm, 3um; Mobile Phase A: CO2, Mobile Phase B : IPA (0.1% 7 M NHs-methanol); Flow rate: 90 mL / min; Gradient (B%): isocratic 20% B; Back Pressure(bar): 100; Wave Length: 220 nm; RTl(min): 3.55; RT2(min): 4.28; Sample Solvent: methanol; Injection Volume: 3 mL) to afford the single isomer (180 mg) as a yellow solid.

[0675] STEP 6

[0676] A solution of the product from step 5 (60 mg, 0.127 mmol), K3PO4 (161 mg, 0.762 mmol), Pd(dppf)C12-DCM (20.70 mg, 0.025 mmol) and potassiumPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 cyclopropyltrifluoroboranuide (38 mg, 0.254 mmol) in toluene (1.2 mL) and H2O (0.4 mL) was stirred at 110°C overnight under nitrogen. The resulting mixture was concentrated under reduced pressures and extracted with DCM (2 x 10 mL), and dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure to afford the product (40 mg, 81%) as a brown oil.

[0677] STEP 7

[0678] A solution of the product from step 6 (50 mg, 0.129 mmol) and HC1 in 1,4-dioxane (4.0 M) (10 mL) in methanol (1 mL) was stirred at RT for 2 h. After concentration, the crude product was purified by Prep-HPLC with the following conditions (Column: XSelect CSH Prep Phenyl -Hexyl Column 19*250 mm, 5pm; Mobile Phase A: water (10 mmol / L NH4HCO3), Mobile Phase B: methanol; Flow rate: 20ml / min; Gradient (B%): 22% B to 42% B in 10 min; Wave Length: 254nm / 220nm; RTl(min): 8) to afford 83 (12 mg, 28%) as an off-white solid. [M+H]+(ESI):288.1 'HNMR (400 MHz, Methanol-d4) 5 8.46 (s, 1H), 6.23 (s, 1H), 3.75 (d, J = 2.5 Hz, 6H), 3.71 - 3.60 (m, 1H), 3.27 - 3.20 (m, 1H), 3.12 - 3.02 (m, 1H), 2.89 - 2.71 (m, 2H), 2.61 - 2.49 (m, 1H), 2.40 - 2.31 (m, 1H), 2.21 - 2.12 (m, 1H), 1.83 - 1.65 (m, 1H), 1.02 - 0.84 (m, 6H), 0.71 - 0.63 (m, 2H).

[0679] Preparation of Compound 82

[0680] Compound 82 was prepared analogously to 83 beginning with the corresponding enantiomer and exhibited identical spectral properties to 83.

[0681] Preparation of Compound 84

[0682] A solution of of the starting amine (20 mg, 0.081 mmol), DIEA (42.25 uL, 0.243 mmol) and 2-fluoroidoethane (137 mg, 0.810 mmol) in acetonitrile (1 mL) was stirred at 80°C for overnight under nitrogen. After concentration, the crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 7% B to 25% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 8.67) to afford 84 (11 mg, 40%) as a white solid. [M+H]+(ESI):294.1 'H NMR (300 MHz, methanol- tZ4) 5 8.51 (s, 1H), 6.23 (s, 1H), 4.70 - 4.61 (m, 1H), 3.75 (d, J= 2.4 Hz, 6H), 3.50 - 3.40 (m, 1H), 3.37 - 3.31 (m, 1H), 3.22 - 3.12 (m, 1H), 3.10 - 3.01 (m, 1H), 2.81 - 2.61 (m, 1H), 2.55PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699- 2.40 (m, 1H), 2.31 - 2.22 (s, 1H), 2.20 - 2.09 (m, 1H), 1.83 - 1.59 (m, 1H), 1.37 - 1.19 (m,1H),1.O3 - 0.88 (m, 2H), 0.72 - 0.61 (m, 2H).

[0683] Preparation of Compound 85

[0684] Compound 85 was prepared analogously to 84 beginning with the corresponding enantiomer and exhibited identical spectral properties to 84.

[0685] Preparation of Compound 86

[0686] STEP 1

[0687] A solution of the protected amine (150 mg, 0.32 mmol), Pd(dppf)C12-DCM (56 mg, 0.069 mmol), K3PO4 (441 mg, 2.07 mmol) and potassium cyclopropyltrifluoroboranuide (512 mg, 3.46 mmol) in toluene (1 mL), H2O (0.2 mL) was stirred at 110°C overnight under nitrogen. After filtration, the residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in water (10 mmol / L NH4HCO3), 40% to 90% gradient in 10 min; detector, UV 220 nm to afford the product (120 mg, 49%) as a brown oil. [M+H]+(ESI): 348.20

[0688] STEP 2

[0689] A solution of the product from step 1 (100 mg, 0.23 mmol) and TFA (1 mL) in DCM (3 mL) was stirred at RT for 2 h. The resulting mixture was concentrated under reduced pressure. The crude product (180 mg,: >100%) was used in the next step directly without further purification. [M+H]+(ESI): 248.10

[0690] STEP 3

[0691] A solution of of the product from step 2 (180 mg, 0.73 mmol), DIEA (282 mg, 2.18 mmol) and l-fluoro-2-iodoethane (380 mg, 2.18 mmol) in MeCN (3 mL) was stirred at 70°C overnight under nitrogen. After concentration, the crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH C18 OBD Column 30*150mm 5pmn;PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699Mobile Phase A: water (0.1% FA), Mobile Phase B: MeCN; Flow rate: 60 mL / min; Gradient (B%): 1% B to 26% B in lOmin; Wave Length: 220 nm; RTl(min): 9.38) to afford 86 (22.9 mg, 9%) as an off-white solid. [M+H]+(ESI): 294.10. 'H NMR (300 MHz, CD3OD) 5 6.20 (s, 1H), 4.87-4.83 (m, 1H), 4.79-4.67 (m, 1H), 4.64-4.54 (m, 1H), 3.75 (s, 3H), 3.73 (s, 3H), 3.31- 3.09 (m, 3H), 2.97-2.82 (m, 1H), 2.62-2.44 (m, 2H), 2.26-2.09 (m, 2H), 1.69-1.50 (m, 1H), 1.02-0.90 (m, 2H), 0.72-0.61 (m, 2H).

[0692] Preparation of Compound 88s

[0693] A solution of the starting amine (20 mg, 0.081 mmol), DIEA (42 uL, 0.243 mmol) and 2,2-difluoroethyl trifluoromethanesulfonate (17 mg, 0.081 mmol) in acetonitrile (1 mL) was stirred at 70°C for 24 h under nitrogen. After concentration, the crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep Cl 8 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 9% B to 25% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.68) to afford 88 (13 mg, 46%) as an off-white solid. [M+H]+(ESI):312.1 'H NMR (300 MHz, methanol-A) 5 6.19 (s, 1H), 6.34 - 5.72 (m, 2H), 3.74 (d, J= 1.9 Hz, 6H), 3.38 - 3.28 (m, 1H), 3.27 - 3.20 (m, 1H), 3.18 - 2.96 (m, 3H), 2.77 - 2.58 (m, 1H), 2.41 - 2.02 (m, 3H), 1.66 - 1.46 (m, 1H), 1.02 - 0.87 (m, 2H), 0.71 - 0.58 (m, 2H).

[0694] Preparation of Compound 89

[0695] Compound 89 was prepared analogously to 88 beginning with the corresponding enantiomer and exhibited identical spectral properties to 88.

[0696] Preparation of Compound 90

[0697] PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0698] STEP 1

[0699] A mixture of the Boc protected starting material (200 mg, 0.46 mmol), cyclopent- 1-en- 1-ylboronic acid (62 mg, 0.55 mmol), Pd(dppf)C12 (33 mg, 0.046 mmol) and K3PO4 (293 mg, 1.38 mmol) in toluene (2 mL) and H2O (0.4 mL) was stirred at 110°C overnight under nitrogen. The reaction was diluted with water (5 mL) at RT. The resulting mixture was extracted with EtOAc (3 x 10 mL) and dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in water (10 mmol / L NH4HCO3), 10% to 100% gradient in 10 min; detector, UV 220 nm which afforded the product(130 mg) as a yellow solid. [M+H-56]+(ESI):318.10.

[0700] STEP 2

[0701] A mixture of of the product from step 1 (130 mg, 0.35 mmol) and Pd / C (130 mg, 1.22 mmol) in MeOH (3 mL) was stirred at RT for 1 h under hydrogen. The resulting mixture was filtered and the filter cake was washed with MeOH (3 x 10 mL). The filtrate was concentrated under reduced pressure which afforded the crude product (130 mg, 100%) as a white solid. [M+Na]+(ESI):372.15

[0702] STEP 3

[0703] A mixture of the product from step 2 (100 mg, 0.26 mmol) and HC1 in 1,4-dioxane (4.0 M) (1 mL) in MeOH (1 mL) was stirred at RT for 1 h. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% HC1), Mobile Phase B: MeCN; Flow rate: 60 mL / min; Gradient (B%)5-25; Wave Length: 254nm / 220nm; RTl(min): 9.42) to afford 90 (33 mg, 40%) as a white solid. [M+H]+(ESI):276.15. 'H NMR (400 MHz, CD3OD) 5 6.67 (s, 1H), 3.79 (s, 3H), 3.66 (s, 3H), 3.54-PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26993.40 (m, 1H), 3.40-3.32 (m, 1H), 3.22-3.11 (m, 1H), 3.10-3.02 (m, 1H), 2.85-2.69 (m, 1H), 2.51 (dd, J= 16.9, 9.8 Hz, 1H), 2.07-1.95 (m, 1H), 1.94-1.86 (m, 2H), 1.86-1.73 (m, 2H), 1.73- 1.59 (m, 3H), 1.59-1.48 (m, 2H).

[0704] Preparation of Compound 91

[0705] Compound 91 was prepared analogously to 90 beginning with the corresponding enantiomer and exhibited identical spectral properties to 90.

[0706] Preparation of Compound 92

[0707] A solution of 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-one (100 mg, 0.485 mmol) and 2-(aminomethyl)phenol (66 mg, 0.533 mmol) in dichloromethane (3 mL) was added sodium triacetoxyborohydride (360 mg, 1.698 mmol). The reaction was stirred for 8 h at RT under nitrogen. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (0.1% HC1), 10% to 50% gradient in 10 min; detector, UV 254 nm. to afford 92 (24 mg, 14% yield) as a white solid. MS m / z [M+H]+(ESI):314.15. 'HNMR (300 MHz, Methanol^) d 7.13-7.04 (m, 2H), 6.86-6.71 (m, 2H), 6.67 (s, 2H), 4.01 (s, 2H), 3.75 (s, 3H), 3.74 (s, 3H), 3.17-3.02 (m, 1H), 3.00-2.80 (m, 2H), 2.60-2.28 (m, 2H), 2.19-2.05 (m, 1H), 1.65-1.41 (m, 1H).

[0708] Preparation of Compound 93

[0709] Compound 93 was prepared anlogouesly to 92 (14 mg, 8%) as a white solid. MS m / z [M+H]+(ESI):328.15. ‘H NMR (300 MHz, Methanol^) d 7.54-7.38 (m, 2H), 7.15-6.97 (m, 2H), 6.76 (s, 2H), 4.33 (s, 2H), 3.94 (s, 3H), 3.79 (s, 3H), 3.77 (s, 3H), 3.56-3.37 (m, 2H), 3.10- 2.98 (m, 1H), 2.72-2.55 (m, 2H), 2.42-2.31 (m, 1H), 1.87-1.73 (m, 1H).

[0710] Preparation of Compounds 100PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0711] STEP 1:

[0712] Into a 50 mL 3 -necked round-bottom flask were added 4,7-dimethoxy-2,3- dihydroinden-l-one (2.5 g, 13.0 mmol) in methanol (10 mL) and concentrated aq. hydrochloric acid (2 mL) followed by the addition of propan-2-yl nitrite (6 mL) at RT. The resulting mixture was stirred at 50°C for 3 h. The reaction mixture was cooled and the precipitated solids were collected by filtration. The solid was washed with ethanol (10 mL x 3) and then dried in vacuum which afforded the product (1.9 g, 66%) as a yellow solid. [M+H]+(ESI): 222.10.

[0713] STEP 2:

[0714] To a solution of of the product from step 1 (500 mg, 2.26 mmol) in ethanol (20 mL) was added 10% Pd / C catalyst (100 mg, water content: 50%) in a pressure vessel. The mixturePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 was purged with nitrogen for 5 min and then was pressurized to 20 atm. with hydrogen at RT for 8 h. The reaction mixture was filtered through a pad of celite. To the filtrate was added sodium borohydride (171 mg, 4.52 mmol, 2 equiv.) portion-wise at 0°C. The resulting mixture was stirred at 0°C for 30 min, quenched with saturated aq. NH4Q solution (10 mL) and extracted with ethyl acetate (20 mL x 3). The combined organic layers were washed with saturated aq. sodium chloride solution (20 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluted with DCM / methanol (5 / 1) to the afford product (250 mg, 52%) as a purple solid. [M+H]+(ESI):210.10.

[0715] STEP 3:

[0716] A solution of product from step 2 (150 mg, 0.72 mmol) in trifluoroacetic acid (20 mL) was treated with EtsSiH (416.78 mg, 3.58 mmol) at RT overnight. The resulting mixture was basified with saturated aq. Na2COs solution until pH = 8-9 and then extracted with ethyl acetate (20 mL x 3). The combined organic layers were washed with saturated aq. sodium chloride solution (10 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (0.1% hydrochloric acid), 10% to 50% gradient in 10 min; detector, UV 220 nm to afford the product (50 mg, 36%) as a white solid. [M+H]+(ESI): 194.10.1H NMR (300 MHz, methanol-A) 5 6.78 (s, 2H), 4.13-4.04 (m, 1H), 3.78 (s, 6H), 3.35 (d, J= 7.5 Hz, 1H), 3.28 (s, 1H), 2.94 (dd, J= 17.0, 3.9 Hz, 2H).

[0717] STEP 4:

[0718] A solution of of the product from step 3 (240 mg, 1.24 mmol) and Ag2SO4 (774 mg, 2.48 mmol) in methanol (3 mL) was added iodine (630 mg, 2.48 mmol) at RT. Then the mixture was stirred for 16 h under nitrogen atmosphere. The resulting mixture was filtered and the filter cake was washed with ethyl acetate (10 mL x 3). The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 50% to 100% gradient in 10 min; detector, UV 220 nm which afforded the product (300 mg, 75%) as a brown solid. [M+H]+(ESI):320.01.

[0719] STEP 5

[0720] A mixture of of the product from sep 4 (120 mg, 0.37 mmol), phthalic anhydride (139 mg, 0.94 mmol) and EtsN (114 mg, 1.13 mmol) in toluene (1.5 mL) was stirred at 110°C overnight. The resulting mixture was cooled to RT and concentrated under reduced pressure.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 60% to 80% gradient in 10 min; detector, UV 220 nm which affoeded the product (55 mg, 32%) as a brown solid. [M+H]+(ESI):450.00.

[0721] STEP 6:

[0722] A mixture of product from step 5 (55 mg, 0.12 mmol) and cuprous cyanide (13 mg, 0.14 mmol) in DMF (2 mL) was stirred at 150°C for 2 h. The reaction was cooled to RT and then diluted with methanol (5 mL). The resulting mixture was filtered and the filter cake was washed with methanol (10 mL x 2). The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 60% to 80% gradient in 10 min; detector, UV 220 nm which affordedthe product (39 mg, 91%) as a brown solid. [M+H]+(ESI):349.11.

[0723] STEP 7:

[0724] A mixture of the product from step 6(34 mg, 0.098 mmol) and hydrazine monohydrate (9 mg, 0.16 mmol, 80% in water) in ethanol (1 mL) was stirred at 80°C for 2 h. The resulting mixture was filtered and the filter cake was washed with methanol (10 mL x 2). The filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 40% to 60% gradient in 10 min; detector, UV 220 nm which afforded the product (20 mg, 93%) as a white solid. [M+H]+(ESI): 219.11.

[0725] STEP 8:

[0726] A mixture of the product from steo 8 (20 mg, 0.092 mmol), 3-chloro-5- methylbenzaldehyde (17 mg, 0.11 mmol) and acetic acid (5 mg, 0.092 mmol) in methanol (1 mL) was added sodium cyanoborohydride (11 mg, 0.18 mmol, 2 equiv.) at room temperature. Then the mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated aq. NH4CI (0.5 mL). The resulting mixture was extracted with DCM (3 mL x 3) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC (Column: Xselect CSH Prep Cl 8 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient: 10% B to 30% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.7) to afford 94 (19 mg, 52% 97%) as a white solid. [M+H]+(ESI): 357.00. 'H NMR (300 MHz, methanol^) 57.29 (s, 1H), 7.21 (d, J= 4.6 Hz, 2H), 7.04 (s, 1H), 4.01 (s, 2H), 3.94 (s, 4H), 3.83 (s, 3H), 3.49 - 3.34 (m, 2H), 2.97 - 2.89 (m, 2H), 2.36 (s, 3H).PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0727] STEP 9

[0728] The racemic 94 (12 mg) was sepearated by Chiral -HPLC with the following conditions (Column: CHIRALPAK IF 2*25 cm, 5 pm; Mobile Phase A: HEX (0.5% 2M NH3-methanol), Mobile Phase B: ethanol; Flow rate: 20 mL / min; Gradient (B%): isocratic 20; Wave Length: 220 / 254 nm; RTl(min): 8.191; RT2(min): 9.839; Sample Solvent: ethanol; Injection Volume: 0.4 mL; Number of Runs: 6) to afford 125 (2.8 mg, 23%) as a white solid. [M+H]+(ESI): 357.00.JH NMR (400 MHz, methanol-A) 5 7.41 - 7.22 (m, 3H), 7.10 (s, 1H), 4.16 (t, J= 7.5 Hz, 3H), 3.97 (s, 3H), 3.85 (s, 3H), 3.66 - 3.51 (m, 1H), 3.43 (d, J = 8.1 Hz, 1H), 3.23-3.19 (m, 1H), 3.14-3.10 (m, 1H), 2.38 (s, 3H)

[0729] Comopound 126 exhibited identical spectral properties to 125.

[0730] Preparation of Compound 95

[0731] Compoound 95 was prepared analogously to 94. (524 mg, 48% yield) as a white solid. [M+H]+(ESI):316.05. H NMR (400 MHz, methanol-^) 5 7.18 (s, 1H), 7.14 - 7.09 (m, 1H), 7.08 - 7.01 (m, 1H),6.78 (s, 2H), 4.26 (s, 2H), 4.19 - 4.07 (m, 1H), 3.78 (s, 6H), 3.52 - 3.37 (m, 2H), 3.11 - 2.98 (m, 2H), 2.42 - 2.38 (m, 3H).

[0732] Preparation of Compound 96

[0733] Compound 96 was prepared analogously to 92. (2.2 mg) as a white solid. LCMS [M+H]+ (ESI): 315. ‘HNMR (400 MHz, Methanol-d4) 57.80 (d, J=6.8Hz, 1H), 7.56-7.54 (m, 1H), 6.75 (s, 2H), 6.48-6.44 (m, 1H), 4.23 (s, 2H), 3.77 (d, J=4.8Hz, 6H), 3.55-3.48 (m, 1H), 3.35-3.32 (m, 1H), 3.06-2.99 (m, 1H), 2.70-2.60 (m, 2H). 2.38-2.33 (m, 1H), 1.87-1.77 (m, 1H).

[0734] Preparation of Compound 97

[0735] STEP 1

[0736] To a stirred solution of 6-methyl-2-oxo-lH-pyridine-3-carbonitrile (200 mg, 1.491 mmol) and ammonium hydroxide (28% in water) (500 uL) in methanol (10 mL) was added Raney nickel (200 mg, 3.414 mmol) at RT. The resulting mixture was stirred at 50 °C for additional 18 h under hydrogen atmosphere. The resulting mixture was filtered; the filter cake was washed with methanol (3 x 30 mL). The filtrate was concentrated under reduced pressure.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699The crude product was used in the next step directly without further purification(190 mg, 92% yield).

[0737] STEP 2

[0738] Compound 97 prepared from the product of step 1 according to procedure described for 92. (26 mg, 14%) as an off-white solid. LCMS[M+H]+ (ESI):329.10. H NMR (300 MHz, Methanol-d4) 5 7.69 (d, J= 7.1 Hz, 1H), 6.77 (s, 2H), 6.28 (dd, J= 7.1, 0.9 Hz, 1H), 4.21 (s, 2H), 3.79 (d, J = 3.6 Hz, 6H), 3.58 - 3.49 (m, 1H), 3.41 - 3.27 (m, 1H), 3.04 (ddd, J = 17.9, 5.7, 4.0 Hz, 1H), 2.76 - 2.57 (m, 2H), 2.35 (d, J= 0.8 Hz, 3H), 1.83 (dtd, J= 12.5, 11.2, 5.6 Hz, 1H).

[0739] Preparationn of Compounnd 98

[0740] Compound 98 was prepared analogously to 92 (18 mg) as a white solid. LCMS [M+H]+(ESI): 329. *H NMR (300 MHz, Methanol-d4) 5 8.49 (s, 1H), 8.23-8.21 (m, 1H), 7.83-7.80 (m, 1H), 7.06-7.02 (m, 1H), 6.75 (s, 2H),4.29 (s, 2H), 4.03 (s, 3H), 3.78 (d, .7=6 Hz, 6H), 3.51-3.35 (m, 2H), 3.07-2.98 (m, 1H), 2.67-2.56 (m, 2H), 2.37-2.31 (m, 1H), 1.85-1.71 (m, 1H).

[0741] Preparation of Compound 99

[0742] Compound 99was prepared analogously to 97 (3 mg, 1.4%) as a white solid. LCMS [M+H]+ (ESI): 343. >H NMR (300 MHz, Methanol-d4) 5 8.55 (s, 1H), 7.59-7.58 (d, 1H), 6.84- 6.82 (d, 1H), 6.70 (s, 2H), 4.01-3.99 (d, 5H), 3.77-3.76 (d, 6H), 3.25 - 3.12 (m, 1H), 3.10 (s, 1H), 2.92-2.97 (m, 1H), 2.63 - 2.42 (m, 1H), 2.43 (s, 3H), 2.19-2.23 (m, 1H), 1.60-1.64 (m, 1H).

[0743] Preparation of Compound 100

[0744] Compound 100 was prepared analogously to 94. (6 mg, 21%) as a white solid. [M+H]+(ESI):341.05. H NMR (400 MHz, methanol-^) 5 7.07 - 6.72 (m, 4H), 3.94 (d, J = 5.7 Hz, 5H), 3.82 (s, 4H), 3.38 (dd, J= 16.5, 7.7 Hz, 1H), 3.25 (d, J= 7.7 Hz, 1H), 2.99 (dd, J= 16.5, 6.1 Hz, 1H), 2.88 (dd, J= 17.3, 6.0 Hz, 1H), 2.36 (s, 3H).

[0745] Preparation of Compound 101

[0746] Compound 101 was prepared analogously to 92 (6 mg, 18) as a white solid. [M+H]+(ESI):315.10.1H NMR (300 MHz, Methanol-6 / 4) 3 8.42-8.31 (m, 1H), 7.90-7.71 (m, 2H), 6.76 (s, 2H), 4.66 (s, 2H), 3.78 (d, J= 5.7 Hz, 6H), 3.65 (s, 1H), 3.48-3.35 (m, 1H), 3.01-3.10 (m, 1H), 2.59-2.70 (m, 2H), 2.44 (d, J= 12.3 Hz, 1H), 1.87 (qd, J= 11.7, 5.5 Hz, 1H).

[0747] Preparation of Compound 102

[0748] Compound 102 was prepared analogously to 92 (17.3 mg, 48.89% yield, 98.5% purity) as a white solid. [M+H]+ (ESI):329.15. H NMR (300 MHz, Methanol-6 / 4) 3 8.40 (d, J= 4.9 Hz, 1H), 8.04 (d, J = 8.5 Hz, 1H), 7.85 (dd, J = 8.5, 5.0 Hz, 1H), 4.66 (s, 2H), 4.10 (s, 3H),PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26993.78 (d, J= 6.4 Hz, 7H), 3.41 (dd, J= 16.5, 4.9 Hz, 1H), 2.98-3.12 (m, 1H), 2.68-2.78 (m, 2H), 2.45 (d, J= 12.3 Hz, 1H), 1.89 (qd, J= 11.5, 5.0 Hz, 1H).

[0749] Preparation of Compound 103

[0750] Compound 103 was prepared analogously to 92 (22 mg, 26%) as a orange solid. [M+H]+(ESI):302.20. ‘HNMR (300 MHz, Methanol-^) 8 7.79 (s, 1H), 7.62 (s, 1H), 6.75 (s, 2H), 4.25 (s, 2H), 3.91 (s, 3H), 3.77 (d, J= 5.1 Hz, 6H), 3.52-3.40 (m, 1H), 3.27-3.35 (m, 1H),3.O6 - 2.97 (m, 1H), 2.67 - 2.56 (m, 2H), 2.35 - 2.25 (m, 1H), 1.91 - 1.71 (m, 1H).

[0751] Preparation of Compound 104

[0752] Compound 104 was prepared analogously to 92 (5 mg, 3%) as orange semi-solid. [M+H]+(ESI):285.15. ‘H NMR (300 MHz, Methanol-^) 6 7.88 -7.87 (m, 1H), 7.51 - 7.50(m,lH), 6.72-6.63 (m, 4H), 3.99 - 3.96 (m,lH), 3.75 (d, J = 4.5 Hz, 6H), 3.24-3.10 (m, 1H), 2.93 - 2.85(m,lH), 2.72 -2.69 (m,lH), 2.45 (dd, J= 17.0, 9.0 Hz, 1H), 2.15 - 2.10(m,lH), 1.70 - 1.63 (m,lH).

[0753] Preparation of Compound 105

[0754] Compound 105 was prepared analogously to 92 (4 mg, 4%) as a white solid. [M+H]+(ESI):286.25. ‘H NMR (300 MHz, Methanol-^) 6 8.26 (d, J= 4.9 Hz, 2H), 6.68 (s, 2H), 6.59 (t, .7= 4.9 Hz, 1H), 4.17-4.02 (m, 1H), 3.75 (d, = 4.3 Hz, 6H), 3.15 (dd, J= 17.1, 5.3 Hz, 1H), 2.98-2.83 (m, 1H), 2.67-2.65 (m, 1H), 2.53-2.38 (m, 1H), 2.19-2.06 (m, 1H), 1.71 -1.67 (m,lH).

[0755] Preparation of Compound 106

[0756] Compound 106 was prepared analogously to 92 (47 mg, 54%) as a white solid. MS m / z [M+H]+(ESI): 315.10. ‘HNMR (300 MHz, DMSO-t / ,) 6 8.20 (s, 1H), 7.28 (d, = 6.7 Hz, 1H), 6.68 (s, 2H), 6.31 (s, 1H), 6.20 (dd, J = 6.7, 1.6 Hz, 1H), 4.05 (br, 1H), 3.70 (d, J = 3.3 Hz, 6H), 3.66 (s, 2H), 3.03 - 2.84 (m, 1H), 2.84 - 2.64 (m, 2H), 2.48 - 2.32 (m, 1H), 2.25 (dd, J= 17.0, 9.0 Hz, 1H), 1.98 (d, J= 12.7 Hz, 1H), 1.50 - 1.32 (m, 1H).

[0757] Preparation of Compound 107

[0758] Compound 107 was prepared analogously to 92 (30 mg, 34%) as a white solid. MS m / z [M+H]+(ESI): 315.15. ‘HNMR (300 MHz, DMSO-t / ,) 6 8.27 (s, 1H), 7.49 (dd, J= 9.4, 2.1 Hz, 1H), 7.42 - 7.21 (m, 1H), 6.69 (s, 2H), 6.30 (d, J= 9.3 Hz, 1H), 3.70 (d, J= 2.7 Hz, 6H), 3.08 - 2.62 (m, 3H), 2.48 - 2.35 (m, 1H), 2.29 (dd, J= 16.7, 8.8 Hz, 1H), 2.08 - 1.97 (m, 1H), 1.57 - 1.31 (m, 1H).

[0759] Synthesis of Compound 110

[0760] Compound 110 was prepared analogously to 109 from 113 and 3-fluoro-5- methylbenzaldehyde (48%) as a white solid. [M+H]+(ESI):316.05 'H NMR (400 MHz,PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 methanol-A) 5 7.18 (s, 1H), 7.14 - 7.09 (m, 1H), 7.08 - 7.01 (m, 1H),6.78 (s, 2H), 4.26 (s, 2H), 4.19 - 4.07 (m, 1H), 3.78 (s, 6H), 3.52 - 3.37 (m, 2H), 3.11 - 2.98 (m, 2H), 2.42 - 2.38 (m, 3H).

[0761] Synthesis of Compound 112l

[0762] STEP 1 :

[0763] Into a 100 mL round-bottom flask were added the starting hydrazine (0.60 g, 5.50) and N-Cbz glycine (1.27 g, 6.05 mmol) and toluene (15 mL) at RT. The resulting mixture was stirred at 130°C for 20 h under nitrogen, after which the solvent was all evaporated in vacuo. The residue was re-crystallized from ethyl acetate (15 mL) to afford the product(0.67 g, 43%) as an off-white solid. [M+H]+(ESI):283.10.

[0764] STEP 2:

[0765] Into a 40 mL vial were added the product from step 1 (668 mg, 2.37 mmol) and hydrogen bromide-acetic acid solution (5.7 M) (2.08 mL, 11.83mmol) and AcOH (10 mL) at RT. The resulting mixture was stirred at 90°C for 3 h under nitrogen. The resulting mixture was diluted with diethyl ether (10 mL). The precipitated solids were collected by filtration and washed with diethyl ether (2 x 10 mL) which afforded the product (600 mg, 99%) as an off- white solid. [M+H]+(ESI): 149.05.

[0766] STEP 3

[0767] To a 8 mL vial were added the product from step 1 (50 mg, 0.218 mmol) and NaOH (9) mg, 0.218 mmol). After stirring briefly, the resulting mixture was concentrated under reduced pressure. To the above mixture was added 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26992-one (45 mg, 0.218 mmol), NaBHsCN (41mg, 0.654 mmol), methanol (0.5 mL) and AcOH (12.5 uL, 0.218 mmol, .) at room temperature. The resulting mixture was stirred at 0°C for 1 h under nitrogen atmosphere. The reaction was quenched with saturated aq. NH4Q (1 mL) at 0°C. The mixture was basified to pH 9~10 with a.q. ammonia (2 mL). The resulting mixture was extracted with DCM (3 x 3 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient: 3% B to 18% B in 10 min; Wave Length: 254nm / 220nm; RTl(min): 8.63 which afforded 112 (15 mg, 17%) as a white solid. [M+H]+(ESI):339.10. 'H NMR (400 MHz, methanol-A) 5 8.53 (d, J= 7.1 Hz, 1H), 8.36 (br, 1H), 7.73 (d, J = 9.4 Hz, 1H), 7.48 (dd, J= 9.3, 6.6 Hz, 1H), 7.03 (t, J = 6.8 Hz, 1H), 6.67 - 6.65 (m, 2H), 4.61 (s, 2H), 3.74 - 3.73 (m, 6H), 3.19 - 3.06 (m, 2H), 2.91 (dt, J= 17.8, 4.9 Hz, 1H), 2.58 - 2.49 (m, 1H), 2.47 - 2.40 (m, 1H), 2.23 - 2.12 (m, 1H), 1.67 - 1.57 (m, 1H).

[0768] Synthesis of Compound 113

[0769] Compound 113 was prepard according to Step 3 of the 112 preparation using 1H- indazole-3-carbaldehyde and 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-one which affored (17 mg, 29%) as a white solid. [M+H]+(ESI):338.05. 'H NMR (300 MHz, methanol-A) 5 7.88 - 7.86(m, J= 8.2, 1.0 Hz, 1H), 7.57 - 7.54 (m, 1H), 7.49 - 7.38 (m, 1H), 7.25 - 7.22(m, 1H), 6.74 (s, 2H), 4.66 (s, 2H), 3.77 (d, J= 5.3 Hz, 6H), 3.55 - 3.33 (m, 2H), 3.09 - 2.95 (m, 1H), 2.60 (dd, J= 16.0, 10.0 Hz, 2H), 2.42 - 2.31 (m, 1H), 1.78 - 1.72 (m, 1H).

[0770] Synthesis of Compound 114

[0771] Compound 114 was prepard according to Step 3 of the 112 preparation using 1-(1,2- benzoxazol-3-yl)methanamine hydrochloride and 5,8-dimethoxy-3,4-dihydro-lH-naphthalen- 2-one which afforeded 17 mg (30%) as an off-white semi-solid. [M+H]+(ESI):339.15. 'H NMR (300 MHz, methanol-d4) 5 8.50 (s, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.65 (t, J = 3.3 Hz, 2H), 7.64-7.38 (m, 1H), 6.68 (s, 2H), 4.57 (s, 2H), 3.75 (s, 3H), 3.74 (s, 3H), 3.32-3.31 (m, 1H), 3.30-2.94 (m, 1H), 2.592.25 (m, 3H), 1.73-1.63 (m, 1H).

[0772] Synthesis of Compound 115

[0773] Compound 115 was prepard according to Step 3 of the 112 preparation using imidazo[l,5-a]pyridine-3-carbaldehyde and 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-one which afforeded 11 mg (13%) yield as a brown solid. [M+H]+(ESI):338.1.1HNMR (300 MHz, methanol-A) 5 8.39 (s, 1H), 8.31 (d, J= 7.1 Hz, 1H), 7.64 - 7.54 (m, 1H), 7.48 (s, 1H), 6.95 -PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26996.87 (m, 1H), 6.85 - 6.75 (m, 1H), 6.73 (s, 2H), 4.71 (s, 2H), 3.76 (d, J= 2.3 Hz, 6H), 3.44 (s, 1H), 3.10 - 2.89 (m, 1H), 2.72 - 2.45 (m, 2H), 2.41 - 2.18 (m, 1H), 1.83 - 1.64 (m, 1H).

[0774] Synthesis of Compound 116

[0775] A solution of of the starting amine (60 mg, 0.246 mmol) in methanol (1 mL) was treated with EtsN (34 uL, 0.246 mmol) at RT for 3 min under nitrogen followed by the addition of HOAc (12 uL, 0.205 mmol) dropwise. To the above mixture was added 3H-l,3-benzodiazole- 4-carbaldehyde (30 mg, 0.205 mmol). The resulting mixture was stirred at RT for additional 15 min. To the above mixture was added sodium cyanoborohydride (26 mg, 0.410 mmol) at 0°C. The resulting mixture was stirred for an additional 3 h. After concentration, the residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm which afforded 116 (13 mg, 16% yield) as a white solid. [M+H]+(ESI):338.0. 'H NMR (300 MHz, methanol-A) 5 8.42 (s, 1H), 8.30 (s, 1H), 7.71 - 7.62 (m, 1H), 7.42 - 7.37 (m, 2H), 6.74 (s, 2H), 4.73 (s, 2H), 3.77 (d, J= 3.3 Hz, 6H), 3.66 - 3.50 (m, 1H), 3.38 - 3.29 (m, 1H), 3.04 - 2.97 (m, 1H), 2.77 - 2.51 (m, 2H), 2.47 - 2.32 (m, 2H), 1.92 - 1.73 (m, 1H).

[0776] Preparation of Compound 1117

[0777] Compound 117 was prepared analogously to 116 (22 mg, 42%) as a brown semi-solid. [M+H]+(ESI):339.1. 'H NMR (300 MHz, methanol-A) 5 8.45 (s, 1H), 7.67 - 7.54 (m, 1H), 7.48 - 7.35 (m, 2H), 6.65 (s, 2H), 4.27 (s, 2H), 3.74 (d, J= 4.5 Hz, 6H), 3.21 - 3.04 (m, 1H), 2.97 - 2.75 (m, 2H), 2.53 - 2.25 (m, 2H), 2.22 - 2.07 (m, 1H), 1.65 - 1.42 (m, 1H).

[0778] Preparation of Compound 118

[0779] Compounds 118 was prepared analogously to 116 (8 mg, 15%) as a brown semi-solid. [M+H]+(ESI):339.1. 'H NMR (400 MHz, methanol-A) 5 8.41 (s, 1H), 7.74 - 7.65 (m, 1H), 7.68 - 7.58 (m, 1H), 7.43 - 7.32 (m, 2H), 6.68 (s, 2H), 4.35 (s, 2H), 3.74 (s, 6H), 3.24 - 3.06 (m, 2H), 2.97 - 2.81 (m, 1H), 2.63 - 2.47 (m, 1H), 2.44 - 2.34 (m, 1H), 2.21 - 2.11 (m, 1H), 1.67 - 1.53 (m, 1H).PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0780] Preparation of Compound 131

[0781] Compound 131was prepared analoguously to 116, (27 mg, 42%) as a white solid. [M+H]+(ESI):365.15. 'HNMR (300 MHz, DMSO-t / e) 5 12.65 (d, J= 6.0 Hz, 1H), 9.25 (d, J = 24.6 Hz, 2H), 8.09 (dd, J= 7.2, 5.8 Hz, 1H), 7.86 - 7.61 (m, 2H), 7.47 (dd, J= 7.1, 1.4 Hz, 1H), 6.77 (s, 2H), 6.28 (d, J= 7.2 Hz, 1H), 4.78 - 4.48 (m, 2H), 3.89 - 3.62 (m, 6H), 3.23 (dd, J = 17.0, 5.3 Hz, 1H), 3.01 - 2.83 (m, 1H), 2.80 - 2.62 (m, 1H), 2.62 - 2.53 (m, 1H), 2.40 - 2.21 (m, 1H), 1.89 - 1.69 (m, 1H).

[0782] Preparation of Compound 119

[0783] STEP 1

[0784] A solution of 5-iodopyridin-2-ol (1 g, 4.5 mmol) in THF (8 mL), H2O (2 mL) was treated with 2-formylphenylboronic acid (0.81 g, 5.43 mmol) at RT followed by the addition of Pd(PPh3)4(523 mg, 0.453 mmol), Na2CO3(959 mg, 9.05 mmol). The resulting mixture was stirred at 70°C overnight under nitrogen. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL x 3). The combined organic layers were concentrated in vacuum to give a residue. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (0.1% NEE.H2O), 10% to 50% gradient in 10 min; detector, UV 254 nm to afford the product (400 mg, 44%) as a light yellow solid. [M+H]+(ESI):200.1

[0785] STEP 2

[0786] A solution of the product from step 1 (33 mg, 0.136 mmol) in methanol (1 mL) was treated with Et3N (23 uL, 0.163 mmol at RT for 3 min under nitrogen followed by the addition of HO Ac (23 uL, 0.408 mmol) dropwise. To the above mixture was added the amine (5 mg, 0.034 mmol) and the resulting mixture was stirred at room temperature for additional 15 min. Sodium cyanoborohydride (17.08 mg, 0.272 mmol, 2 equiv.) was added at 0°C. The resulting mixture was stirred at room temperature for additional 3 h. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep Cl 8 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min;PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699Gradient: 7% B to 23% B in 10 min; Wave Length: 254nm / 220nm; RTl(min): 9.27) to afford 119 (22 mg, 42% yield) as a brown semi-solid. [M+H]+(ESI):391.1. 'H NMR (400 MHz, methanol-A) 5 8.45 (s, 1H), 7.71 - 7.62 (m, 2H), 7.57 - 7.46 (m, 3H), 7.43 - 7.35 (m, 1H), 6.72 (s, 2H), 6.66 (d, J= 9.3 Hz, 1H), 4.38 - 4.25 (m, 2H), 3.76 (d, J= 12.4 Hz, 6H), 3.17 - 3.07 (m, 1H), 3.01 - 2.93 (m, 1H), 2.59 - 2.47 (m, 1H), 2.40 - 2.33 (m, 1H), 2.22 - 2.13 (m, 1H), 1.64 - 1.51 (m, 1H).

[0787] Preparation of Compound 120

[0788] Compound 120 was prepared analoguesly to 94 0 (7 mg, 19%) as a light yellow solid. [M+H]+(ESI):315.0.1HNMR (300 MHz, Methanol^) 5 8.31 - 8.22 (m, 1H), 7.81 - 7.72 (m, 1H), 7.65 - 7.55 (m, 1H), 6.79 (s, 2H), 4.47 (s, 2H), 4.32 - 4.15 (m, 1H), 4.00 (s, 3H), 3.79 (s, 6H), 3.52 - 3.35 (m, 2H), 3.17 - 3.03 (m, 2H).

[0789] Preparation of Compound 121

[0790] Compound 121 was prepared analoguesly to 119 (9 mg, 20%) as a white solid. [M+H]+(ESI):377.0. 'HNMR (400 MHz, methanol-A) 5 7.92 - 7.83 (m, 1H), 7.78 (d, J= 2.5 Hz, 1H), 7.71 - 7.64 (m, 1H), 7.61 - 7.50 (m, 2H), 7.44 - 7.38 (m, 1H), 6.94 (d, J= 9.2 Hz, 1H), 6.76 (s, 2H), 4.26 (s, 2H), 4.17 - 4.06 (m, 1H), 3.77 (s, 6H), 3.37 - 3.33 (m, 1H), 3.27 - 3.24 (m, 1H), 2.89 (m, 2H), 1.33 - 1.14 (m, 3H), 0.91 - 0.82 (m, 1H).

[0791] Preparation of Compound 122PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0792] STEP 1

[0793] A mixture of 2,4,5-trimethoxybenzaldehyde (10 g, 51 mmol), malonic acid (9.55 g, 91.7 mmol) and piperidine (1.69 g, 19.9 mmol) in pyridine (80 mL) was stirred at 80°C overnight. The resulting mixture was cooled to RT and then concentrated under reduced pressure. The residue was diluted with water (200 mL) and then acidified to pH = 3 with concentrated hydrochloric acid. The resulting mixture was extracted with ethyl acetate (100 mL x 3). The combined organic layers were washed with saturated aq. sodium chloride solutionPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699(50 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure to afford the product (10 g, 71%) as a light yellow solid. [M+H]+(ESI): 239.05.

[0794] STEP 2

[0795] A mixture of the product from step 1 (10 g, 42 mmol) and 10% Pd / C catalyst (3.35 g, water content: 50%) in methanol (150 mL) was stirred at RT for 48 h under hydrogen (10 atm.). The resulting mixture was filtered and the filter cake was washed with methanol (100 mL x 3). The filtrate was concentrated under reduced pressure to afford the product (10 g, 99 %) as a white solid. [M+H]+(ESI): 241.10.

[0796] STEP 3

[0797] A mixture of of the product from step 2 (9 g, 37 mmol) and TFAA (39.3 g, 187.3 mmol) in trifluoroacetic acid (20 mL) was stirred at 50°C for 1 h. The resulting mixture was cooled to RT and concentrated under reduced pressure. The residue was basified with saturated aq. NaHCCh solution until pH = 8-9 at 0°C. The resulting mixture was extracted with ethyl acetate (200 mL x 3). The combined organic layers were washed with saturated aq. sodium chloride solution (100 mL) and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 40% to 60% gradient in 10 min; detector, UV 220 nm to afford the product (1.1 g, 13% yield) as a white solid. [M+H]+(ESI): 222.95.

[0798] STEP 4

[0799] A mixture of of the product from step 3 (1.1 g, 4.95 mmol) and isoamyl nitrite (0.87 g, 7.42 mmol) in methanol (10 mL) was added concentrated hydrochloric acid (0.8 mL). Then the mixture was stirred at 50°C for 5 min under nitrogen. After cooled to RT, the precipitated solids were collected by filtration and washed with ethanol (10 mL x 3) which afforded the product (850 mg, 68%) as a yellow solid. [M+H]+(ESI):252.00.

[0800] STEP 5

[0801] A mixture of the product from step 4 (800 mg, 3.18 mmol), concentrated hydrochloric acid (232 mg, 6.36 mmol) and 10% Pd / C catalyst (300 mg, water content: 50%) in ethanol (20 mL) was stirred at RT overnight under 5 atm. hydrogen. The resulting mixture was filtered through a pad of celite and the filter cake was washed with methanol (50 mL x 3). The filtrate was concentrated under reduced pressure which the product (700 mg, 80%) as a yellow solid. [M+H]+(ESI): 238.05.

[0802] STEP 6PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0803] A mixture of the product from step 5 (950 mg, 3.47 mmol) and NaBJHU (525 mg, 13.88 mmol) in methanol (10 mL) was stirred at RT for 2 h. The reaction was quenched with 1 M hydrochloric acid (1 ml). The resulting mixture was concentrated under reduced pressure to remove most of the solvent. The residue was basified with NH3-H2O until pH = 8-9 and purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 5% to 20% gradient in 10 min; detector, UV 220 nm to afford the product (320 mg, 38%) as a yellow solid. [M+H]+(ESI): 240.10.

[0804] STEP 7

[0805] A mixture of the product from step 6 (100 mg, 0.42 mmol), Et:iN (127 mg, 1.25 mmol) and TFAA (263 mg, 1.25 mmol) in DCM (3 mL) was stirred at RT for 1 h. The reaction was quenched with saturated aq. NaHCCh solution (3 mL). The resulting mixture was extracted with CH2CI2 (10 mL x 3). The combined organic layers were washed with saturated aq. sodium chloride solution (10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure to afford the product (130 mg, 92% yield) which was used in the next step directly without further purification. [M+H]+(ESI):336.15.

[0806] STEP 8

[0807] A mixture of the product from step 7 (100 mg, 0.30 mmol), EtiSiH (69 mg, 0.60 mmol) and BF3-Et2O (84 mg, 0.60 mmol) in DCE (2 mL) was stirred at 80°C for 2 h. The reaction was quenched with saturated aq. NaHCCh solution (3 mL). The resulting mixture was extracted with DCM (10 mL x 3). The combined organic layers were washed with saturated aq. sodium chloride solution (5 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 10% to 100% gradient in 10 min; detector, UV 220 nm which afforded the product (70 mg, 73%) as a yellow solid. [M+H]+(ESI):320.10.

[0808] STEP 9

[0809] A mixture of the product from step 8 (50 mg, 0.16 mmol) and K2CO3 (64 mg, 0.47 mmol, 3 equiv.) in methanol (2 mL) was stirred at 80°C for 1 h. The reaction mixture was filtered and the filtrate was concentrated in vacuum to give a residue. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3), 10% to 100% gradient in 10 min; detector, UV 220 nm which afforded (30 mg, 85%) as a white solid. [M+H]+(ESI): 224.10

[0810] STEP 10PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0811] A mixture of the product from step 9 (30 mg, 0.13 mmol), 3-fluoro-5- methylbenzaldehyde (19 mg, 0.13 mmol), sodium cyanoborohydride (16 mg, 0.27 mmol) and acetic acid (8 mg, 0.13 mmol) in methanol (1 mL) was stirred at RT for 1 h. The reaction mixture was quenched with saturated aq. NH4Q solution (0.1 mL) and concentrated in vacuum. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% hydrochloric acid), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 12% B to 25% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.13) to afford 122 (28 mg, 53%) as a white semi-solid. [M+H]+(ESI):346.10. 'HNMR (300 MHz, methanol-A) 5 7.16 (s, 1H), 7.07 (t, J = 10.5 Hz, 2H), 6.56 (s, 1H), 4.25 (s, 2H), 4.11 - 4.08 (m, 1H), 3.89 - 3.73 (m, 6H), 3.70 - 3.65 (m, 3H), 3.53 - 3.37 (m, 2H), 3.12 - 2.96 (m, 2H), 2.40 (s, 3H).

[0812] Preparation of Compound 123

[0813] Compound 123 was prepared from 100 by chiral chrormatography as previously described and exhibited identical spectral characteristics to 100.

[0814] Preparation of Compound 124

[0815] Compound 124 was prepared analogously to 123 exhibited identical spectral characteristics to 100 and 123.

[0816] Preparation of Compound 125

[0817] Compound 125 was prepared from 94 by chiral chrormatography as previously described and exhibited identical spectral characteristics to 94.

[0818] Preparation of Compound 126

[0819] Compound 126 was prepared analogously to 125 exhibited identical spectral characteristics to 94 and 125.

[0820] Preparation of Compound 127

[0821] Compound 124 was prepared analogously to 92 (8 mg, 37%) as a white solid. [M+H]+(ESI):340.00.1H NMR (400 MHz, methanol-A) 5 8.21 (dd, J= 4.8, 1.3 Hz, 1H), 7.54 (dd, J= 8.4, 1.3 Hz, 1H), 7.45 (dd, J= 8.4, 4.7 Hz, 1H), 7.10 (s, 1H), 4.45 (s, 2H), 4.32 - 4.26 (m, 1H), 3.97 (d, J = 4.3 Hz, 6H), 3.85 (s, 3H), 3.61 (dd, J = 17.0, 8.2 Hz, 1H), 3.54 - 3.43 (m, 1H), 3.28 - 3.10 (m, 2H).

[0822] Preparation of 128PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0823] Stepl

[0824] Into a 50 mL 3-necked round-bottom flask were added 8-bromo-2H-isoquinolin-l-one (1.0 g, 4.5 mmol). The flask was evacuated and backfilled with nitrogen for three times. THF (20 mL) was added through a syringe. The mixture was cooled to -70°C. To the above mixture was added 2.5 M n-BuLi (3.9 mL, 9.8 mmol) dropwise. The resulting mixture was stirred at - 70°C for 1 h. To the above mixture was added DMF (0.41 mL, 5.4 mmol) dropwise at -70°C. The resulting mixture was stirred at -70°C for additional 5 min, then warmed up to 0 °C and stirred at 0 °C for 1 h. The reaction was quenched by the addition of saturated NH4Q (aq.) (15 mL) at 0°C. The resulting mixture was extracted with DCM (3 x 10 mL). The combined organic layers were dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was re-crystallized from ethyl acetate / THF (20 mL) (10 / 1, 10 mL) to afford the product (0.30 g, 38% yield) as an off-white solid. [M+H]+(ESI): 174.00.

[0825] STEP 2

[0826] Into an 8 mL vial were added the racemate of compounds 1 / 2 (39 mg, 0.16 mmol), H2O (1 mL), NaOH (6.5 mg, 0.16 mmol) at RT. The resulting mixture was concentrated under vacuum. To the above mixture was added the product of step 1 (35 mg, 0.16 mmol) and sodium cyanoborohydride (30 mg, 0.49 mmol), HO Ac (10 uL, 0.16 mmol) and methanol (1 mL) at RT. The resulting mixture was stirred for 1 h under nitrogen. The reaction was quenched by the addition of saturated NH4Q (aq.) (0.3 mL). The mixture was basified to pH 9 with NH3 H2O. The resulting mixture was extracted with DCM (3 x 3 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xbridge Prep C18 OBD, 30*150mm, 5.0um; Mobile Phase A: water (10 mmol / L NH4HC03+0.05%NH3.H20), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient: 29% B to 44% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 7.17) to afford the freebase. Then 3 eq of 2 M HC1 (aq.) was added and lyophilized to afford 128 (22.1 mg, 34%) as a white solid. [M+H]+(ESI):365.05. 'HNMR (400 MHz, methanol-A) 5 7.86-7.71 (m, 2H),PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26997.61 (dd, J= 7.1, 1.4 Hz, 1H), 7.28 (d, J= 7.1 Hz, 1H), 6.81-6.70 (m, 3H), 4.81-4.67 (m, 2H), 3.82-3.90 (m, 6H), 3.72-3.59 (m, 1H), 3.37 (dd, J = 17.0, 5.3 Hz, 1H), 3.06 (dt, J = 17.9, 4.7 Hz, 1H), 2.80-2.59 (m, 2H), 2.48-2.34 (m, 1H), 1.94-1.78 (m, 1H).

[0827] Preparation of Compound 129

[0828] Compound 129 analogously to 128 (18 mg, 26% yield) as a white solid. [M+H]+(ESI):351.15. 'H NMR (300 MHz, DMSO-t / e) 5 12.83 (s, 1H), 9.33 (s, 2H), 8.21 - 7.99 (m, 1H), 7.92 - 7.63 (m, 2H), 7.48 (d, J= 7.3 Hz, 1H), 6.78 (s, 2H), 6.31 (d, J= 7.2 Hz, 1H), 4.62 (s, 2H), 4.28 - 4.06 (m, 1H), 3.41 - 3.04 (m, 4H).

[0829] Preparation of Compound 130

[0830] Compound 130 was prepared analogously to 128 (18 mg, 29%) as a light yellow solid. [M+H]+(ESI):351.05.XH NMR (400 MHz, methanol-A) 5 7.80 (dd, J= 8.2, 1.4 Hz, 1H), 7.74 (dd, J= 8.1, 7.1 Hz, 1H), 7.58 (dd, J= 7.2, 1.4 Hz, 1H), 7.27 (d, J= 7.1 Hz, 1H), 6.81 - 6.71 (m, 3H), 4.71 (s, 2H), 4.32 - 4.22 (m, 1H), 3.79 (s, 6H), 3.43 (dd, J= 16.8, 8.1 Hz, 2H), 3.22 (dd, J= 16.7, 5.8 Hz, 2H).

[0831] Preparation of Compound 131

[0832] Compound 131was prepared analoguously to 128, (27 mg, 42%) as a white solid. [M+H]+(ESI):365.15. 'HNMR (300 MHz, DMSO-t / e) 5 12.65 (d, J= 6.0 Hz, 1H), 9.25 (d, J = 24.6 Hz, 2H), 8.09 (dd, J= 7.2, 5.8 Hz, 1H), 7.86 - 7.61 (m, 2H), 7.47 (dd, J= 7.1, 1.4 Hz, 1H), 6.77 (s, 2H), 6.28 (d, J= 7.2 Hz, 1H), 4.78 - 4.48 (m, 2H), 3.89 - 3.62 (m, 6H), 3.23 (dd, J = 17.0, 5.3 Hz, 1H), 3.01 - 2.83 (m, 1H), 2.80 - 2.62 (m, 1H), 2.62 - 2.53 (m, 1H), 2.40 - 2.21 (m, 1H), 1.89 - 1.69 (m, 1H).

[0833] Preparation of Compound 145

[0834] A solution of 4 (30 mg, 0.081 mmol) and 2-(chloromethyl)oxirane (75 mg, 0.810 mmol) and DIEA (52 mg, 0.405 mmol) in acetonitrile (3 mL) was stirred at 90°C for 12 h under nitrogen. The crude product (30 mg) was purified by Prep-HPLC with the following conditions (Column: F-phenyl Prep OBD C18 Column, 30*150 mm, 5pm; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 3% B to 10% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.12) to afford 145 (7 mg, 20%) as a colorlessPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 oil. [M+H]+(ESI):389.95. 'HNMR (300 MHz, methanol-d4) 3 8.39 (s, 1H), 7.17 (s, 1H), 4.80- 4.68 (m, 1H), 4.69-4.62 (m, 2H), 4.06-4.01 (m, 2H), 3.79 (s, 3H), 3.71 (s, 3H), 3.60-3.55 (m, 1H), 3.31-3.09 (m, 2H), 2.83-2.77 (m, 1H), 2.46-2.41 (m, 2H), 1.72-1.56 (m, 1H).

[0835] Preparation of Compound 146

[0836] Compounds 146 was prepared analogously to 145 beginning with 6 and exhibited identical spectral preperties to 145.

[0837] Preparation of Compound 1474 W

[0838] To a solution of 4 (30 mg, 0.081 mmol) in acetonitrile (0.3 mL) was added 1,3- dibromopropane (22 mg, 0.108 mmol) and EtsN (36 mg, 0.360 mmol). The mixture was stirred at 80°C for 18 h under nitrogen. The mixture was allowed to cool to RT. The mixture was quenched with water (1 mL), and extracted with DCM (3 x 1 mL). The combined organic layers were dried over anhydrous sodium sulfate. After filtration the filtrate was concentrated under reduced pressure. The residue was purified by Prep-HPLC (Column: Xselect CSH Prep C18 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 11% B to 24% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 8.62) wich afforded 147 (15 mg, 57%) as a yellow solid. [M+H]+(ESI):374.00. H NMR (300 MHz, methanol-d4) 5 7.17 (s, 1H), 4.39 - 4.15 (m, 4H), 3.79 (s, 3H), 3.71 (s, 3H), 3.19 - 2.98 (m, 2H), 2.88 - 2.72 (m, 1H), 2.72 - 2.53 (m, 1H), 2.48 - 2.31 (m, 2H), 2.18 (d, J = 12.4 Hz, 1H), 1.71 - 1.52 (m, 1H).

[0839] Preparation of 148

[0840] Compounds 148 was prepared analogously to 147 beginning with 5 and exhibited identical spectral preperties to 147.

[0841] Preparation of Compound 1494 WPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0842] A solution of 2-methoxypropane-l,3-diol (11 mg, 0.102 mmol) and TfzO (76 mg, 0.272 mmol) in acetonitrile (0.3 mL) was stirred at -25°C for 0.5 h under nitrogen. DIEA (61 mg, 0.476 mmol) was added and the mixture stirred at -25°C for 0.5 h. To the reaction was added 5 (25 mg, 0.068 mmol) and DIEA (61.19 mg, 0.476 mmol) in acetonitrile (0.3 mL) and the resulting mixture was stirred at 70°C for 1.5 h. The mixture was allowed to cool to RT. After concentration, the crude product (40 mg) was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 7% B to 25% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.73) to afford 149 (3.5 mg, 11%) as a colorless oil. [M+H]+(ESI):404.00. 'HNMR (300 MHz, methanol-d4) 3 8.50 (s, 1H), 7.15 (s, 1H), 4.54-4.15 (m, 5H), 3.79 (s, 3H), 3.71 (s, 3H), 3.70-3.59 (m, 1H), 3.40-3.36 (m, 3H), 3.31- 3.02 (m, 2H), 2.28-2.72 (m, 1H), 2.44-2.22 (m, 2H), 1.63-1.28 (m, 1H).

[0843] Preparation of Compound 150

[0844] Compounds 150 was prepared analogously to 149 beginning with 5 and exhibited identical spectral preperties to 149.

[0845] Preparation of Compound 176

[0846] A solution of 4 (20 mg, 0.054 mmol) and benzene, l,2-bis(bromomethyl)benzene (17 mg, 0.065 mmol) and DIEA (28 mg, 0.216 mmol) in toluene (0.4 mL) was stirred at 110°C for 12 h under nitrogen. The mixture was allowed to cool to RT. After concentration, the crude product (30 mg) was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 14% B to 28% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.73) to afford 153 (7.2 mg, 28%) as a colorless oil. [M+H]+(ESI):436.05. 'H NMR (300 MHz, methanol-d4) 3 8.37 (s, 1H), 7.40-7.33 (m, 4H), 7.16 (s, 1H),4.6O (s, 4H), 3.82 (s, 3H), 3.72 (s, 3H), 3.44-3.31 (m, 1H), 3.30-3.08 (m, 2H), 2.86-2.39 (m, 3H), 1.81-1.29 (m, 1H).

[0847] Preparation of Compound 154PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0848] Compounds 154 was prepared analogously to 153 beginning with 5 and exhibited identical spectral properties to 153.

[0849] Preparation of Compound 178

[0850] A solution of 5 (30 mg, 0.081 mmol), DIEA (32 mg, 0.243 mmol) and 2,3- bis(bromomethyl)-pyrazine (32 mg, 0.121 mmol, 1.5) in toluene (1 mL) was stirred at 110°C overnight under nitrogen. After concentration, the crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30* 150mm, 5um; Mobile Phase A: water (0.1% HC1), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 11% B to 24% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.63) to afford 155 (10.1 mg, 34% yield) as a white solid. [M+H]+(ESI): 438. 'H NMR (300 MHz, methanol-A) 5 8.62 (s, 2H), 7.21 (s, 1H), 4.98 (s, 4H), 3.97 - 3.79 (m, 4H), 3.73 (s, 3H), 3.46 - 3.32 (m, 1H), 3.28 - 3.13 (m, 1H), 2.96 - 2.69 (m, 2H), 2.50 (d, J = 12.5 Hz, 1H), 2.01 - 1.81 (m, 1H).

[0851] Preparation of Compound 156

[0852] Compounds 156 was prepared analogously to 155 beginning with 4 and exhibited identical spectral preperties to 155

[0853] Preparation of Compound 157

[0854] A solution of 4 (30 mg, 0.081 mmol) and l,4-dibromobutan-2-ol (38 mg, 0.162 mmol) and KHCO3 (65 mg, 0.648 mmol) in dimethylacetamide (0.6 mL) was stirred at 80°C for 12 h under nitrogen. The mixture was allowed to cool to RT. After filtration, the crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% HC1), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 9% B to 23% B in 8 min; Wave Length: 254nm / 220nm; RTl(min):PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26999.61) to afford 157 (14 mg, 39%) as a white solid. [M+H]+(ESI):404.05. 'H NMR (300 MHz, methanol-d4) 3 7.18 (s, 1H), 4.61-4.53 (m, 1H), 3.86-3.81 (m, 1H), 3.80 (s, 3H), 3.71 (s, 3H), 3.71-3.49 (m, 1H), 3.47 (s, 2H), 3.29-3.07 (m, 2H), 2.81-2.43 (m, 2H), 2.41-2.36 (m, 2H), 2.14- 2.03 (m, 2H), 1.81-1.76 (m, 1H).

[0855] eparation of Compound 158

[0856] Compounds 158 was prepared analogously to 157 beginning with 5 and exhibited identical spectral preperties to 157.

[0857] Preparation of Compound 179

[0858] STEP 1

[0859] A solution of the starting Boc-protected amine (100 mg, 0.231 mmol), 2-[(E)-2- ethoxyethenyl]-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (91 mg, 0.462 mmol) in 1,4-dioxane (0.5 mL) and H2O (0.1 mL) was treated with Na2COs (73 mg, 0.693 mmol) followed by the addition of XPhos Pd G2 (18 mg, 0.023 mmol) at RT. The resulting mixture was stirred at 80°C overnight under nitrogen. The reaction mixture was cooled to RT and then extracted with ethyl acetate (5 mL x 3). The combined organic phases were concentrated in vacuum to give a residue which was purified by Prep-TLC (PEZEA = 4 / 1) to afford the product (50 mg, 57%) as an off- white solid.

[0860] STEP 2

[0861] A mixture of the product from step 1(60 mg, 0.159 mmol) and palladium hydroxide, Pd 5% on carbon powder, nominally 50% water (60 mg) in EtOH (1 mL) was stirred at RT for 3 h under hydrogen (1 atm). The resulting mixture was filtered and the filter cake was washed with EtOH (1 mL x 3). The filtrate was concentrated under reduced pressure to afford the product 2 (50 mg) as an off-white oil.

[0862] STEP 3PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0863] A solution of the product from step 2 (50 mg, 0.132 mmol) and HC1 in dioxane (1.50 mL, 6.00 mmol) in methanol (0.5 mL) was stirred at RT for 2 h under nitrogen. After concentration, the crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% HC1), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): isocratic 5-20; Wave Length: 254 nm / 220 nm; RTl(min): 9.82) to afford 179 (18 mg, 36%) as a white solid. [M+H]+(ESI):280.15. 'H NMR (300 MHz, methanol-d4) 5 8.42 (s, 1H), 8.30 (s, 1H), 7.71-7.62 (m, 1H), 7.42-7.37 (m, 2H), 6.74 (s, 2H), 4.73 (s, 2H), 3.77 (d, J= 3.3 Hz, 6H), 3.66-3.50 (m, 1H), 3.38-3.29 (m, 1H), 3.04-2.97 (m, 1H), 2.77-2.51 (m, 2H), 2.47-2.32 (m, 1H), 1.92-1.73 (m, 1H).

[0864] Preparation of Compound 180

[0865] Compounds 180 was prepared analogously to 179 beginning with the corresponding enantiomer and exhibited identical spectral properties to 179.

[0866] Preparation of Compound 181181

[0867] STEP 1

[0868] To a solution of of the starting Boc-protected amine (30 mg, 0.069 mmol) in toluene (1.2 mL) and H2O (0.3 mL) was added potassium (cyclobutylmethyl)trifluoroboranuide (24 mg, 0.138 mmol), K2CO3 (29 mg, 0.207 mmol) and Ruphos Pd G3 (6 mg, 0.006 mmol). The mixture was stirred at 100°C for 12 h under nitrogen. The mixture was quenched with water (1 mL), then extracted with ethyl acetate (3 x 20 mL). The combined organic layers were dried over anhydrous sodium sulfate. After filtration the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3),PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-26995% to 100% gradient in 10 min; detector, UV 220 nm afforded the product (16 mg, 42%) as a white solid. [M+H]+(ESI):751.50

[0869] STEP 2 The produc from step 1 (15 mg, 0.04 mmol) was dissolved in HCl / di oxane (1.0 mL) and stirred for 1 h at RT. The mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC following the condition (Column: Xselect CSH PrepC18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% HCl), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): 15% B to 30% B in 8 min; Wave Length: 254nm / 220nm; RTl(min): 9.12) to afford 181 (7 mg, 60%) as a white solid. [M+H]+(ESI):276.20. 'HNMR (300 MHz, methanol-d4) 56.60 (s, 1H), 3.78 (s, 3H), 3.66 (s, 3H), 3.56-3.40 (m, 1H), 3.22-2.98 (m, 2H), 2.85-2.44 (m, 5H), 2.31-2.14 (m, 1H), 2.08-1.95 (m, 2H), 1.92-1.54 (m, 5H).

[0870] Preparation of Compound 182

[0871] Compounds 182 was prepared analogously to 181 beginning with the corresponding enantiomer and exhibited identical spectral properties to 182.

[0872] Preparation of Compound 183

[0873] STEP 1

[0874] A mixture of of the starting Boc-protected amine (50 mg, 0.115 mmol), 3-butyn-l-ol(16 mg, 0.230 mmol), Pd(PPh3)2Ch (16 mg, 0.023 mmol), Cui (5 mg, 0.023 mmol) and EtiN (35 mg, 0.345 mmol) in DMSO (1.5 mL) was stirred at 50°C for overnight at RT under nitrogen. The reaction was poured into water and the resulting mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with saturated NaCl (2 x 10 mL), dried over anhydrous Na2SC>4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (10 mmol / L NH4HCO3),PCT / US25 / 44749 03 September 2025 (03.09.2025)Attorney Docket No.: ATAI-115 / 01WO 338067-269910% to 100% gradient in 10 min; detector, UV 220 nm which afforded the productas a colorless oil. [M+H+22]+(ESI):398.10.

[0875] STEP 2

[0876] A mixture of the product from step 1 (50 mg, 0.133 mmol) and 10% Pd / C (28 mg) in methanol (10 mL) was stirred at RT overnight under hydrogen (5 atm). The resulting mixture was filtered and the filter cake was washed with methanol (3 x 10 mL). The filtrate was concentrated under reduced pressure. The crude product (50 mg) was used in the next step directly without further purification.

[0877] STEP 3

[0878] A mixture of the product from step 2 (30 mg, 0.079 mmol) and HC1 in dioxane (0.50 mL, 2.00 mmol) in dioxane (1 mL) was stirred at RT for 1 h. The resulting mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18 OBD, 30*150mm, 5um; Mobile Phase A: water (0.1% HC1), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient (B%): isocratic 3- 20; RTl(min): 8.27) to afford 183 (12 mg, 52%) as a white solid. [M+H]+(ESI):280.05. 'H NMR (400 MHz, methanol-A) 5 6.65 (s, 1H), 3.79 (s, 3H), 3.67 (s, 3H), 3.57 (t, J = 6.4 Hz, 2H), 3.51 - 3.44 (m, 1H), 3.22 - 3.11 (m, 1H), 3.01-3.06 (m, 1H), 2.81-2.72 (m, 1H), 2.69-2.60 (m,2H), 2.54-2.44 (m,lH), 2.23 -2.14 (m, 1H), 1.82 - 1.56 (m, 5H).

[0879] Preparation of Compound 184

[0880] Compounds 184 was prepared analogously to 183 beginning with the corresponding enantiomer and exhibited identical spectral properties to 183.

[0881] Preparation Of 190

[0882] To a solution of 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-one (1.5 g, 7.27 mmol, 1.0 equiv) in dichloromethane (20 mL) was added l-(3-chloro-5-methylphenyl)methanamine (1.24 g, 8.00 mmol, 1.1 equiv) at room temperature under nitrogen atmosphere followed by the addition of sodium triacetoxyborohydride (6.17 g, 29.09 mmol, 4.0 equiv) dropwise at room temperature. The reaction was quenched with water. The aqueous layer was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine (2 x 100 mL), dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated underPCT / US25 / 44749 03 September 2025 (03.09.2025)Attorney Docket No.: ATAI-115 / 01WO 338067-2699 reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in water (0.1% hydrochloric acid), 10% to 50% gradient in 10 min; detector, UV 220 nm. This resulted in 190 (1.059 g) as a white solid. MS m / z [M+H]+(ESI):346.10. 'HNMR (300 MHz, Methanol^) d 7.41 (d, J= 1.9 Hz, 1H), 7.36-7.28 (m, 2H), 6.75 (s, 2H), 4.31 (s, 2H), 3.78 (d, J= 5.6 Hz, 6H), 3.58-3.46 (m, 1H), 3.42-3.32 (m, 1H), 3.11-2.97 (m, 1H), 2.71-2.54 (m, 2H), 2.46-2.31 (m, 4H), 1.87-1.68 (m, 1H).

[0883] Preparation of 191

[0884] Step 1

[0885] A solution of 4-methoxy-2-methylphenol (4.6 g, 33.3 mmol, 1.0 equiv), magnesium chloride (5.0 g, 50.0 mmol, 1.5 equiv), (CH2O)n (3.3 g, 110.0 mmol, 3.2 equiv) and triethylamine (5.0 g, 50.0 mmol, 1.5 equiv) in acetonitrile (25 mL) was stirred at 85°C for 2~3 hours. The reaction mixture was cooled to 25°C and poured into ice-water (200 mL). the resulting mixture was adjusted to pH = 3 with hydrochloric acid (4 N) and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over Na2SC>4, filtered andPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 concentrated to give a crude product which was purified through silica gel column chromatography (petroleum ether : ethyl acetate = 95:5) to afford the crude product (5.0 g, 80%) as a yellow solid. MS m / z [M+H]+(ESI): 167.06.

[0886] Step 2A solution of Crude product from Step 1 (5.0 g, 30.0 mmol, 1.0 equiv), lodomethane (8.5 g, 60.0 mmol, 2.0 equiv) and potassium carbonate (10.0 g) in A( A -di methyl form am ide (20 mL) was stirred at 25°C overnight. The reaction mixture was poured into water (30 mL) and extracted with MTBE (50 mL x 3). The combined organic extracts were washed with water (25 mL), brine (25 mL), dried over Na2SO4 and concentrated to give a crude product which was purified by silica gel column chromatography (petroleum ether : ethyl acetate = 95 : 5) to afford the title product step 2 product (5.2 g, 90%) as a yellow solid. MS m / z [M+H]+(ESI): 181.08.

[0887] Step 3

[0888] To a solution of step 2 product (2.4 g, 13.3 mmol, 1.0 equiv) in tetrahydrofuran (40 mL) was added (2-carboxyethyl)triphenylphosphanium (8.3 g, 20 mmol, 1.5 equiv) and t- BuOK (4.5 g, 40 mmol, 3.0 equiv). The reaction mixture was stirred at room temperature overnight. The solvent was removed, the residue was diluted with water, basified with sodium hydroxide and extracted with ethyl acetate (50 mL). The aqueous phase was adjusted to pH = 2 with aqueous hydrochloric acid and extracted with dichloromethane (30 mL x 3). The combined organic extracts were washed with water (25 mL), brine (25 mL), dried over Na2SO4, filtered and concentrated to give the crude product step 3 (4.48 g) which was used in the next step without further purification. MS m / z [M+H]+(ESI):237.10

[0889] Step 4

[0890] To a stirred solution of crude product of step 3 (4.48 g, 13.2 mmol, 1 equiv) in methanol (20 mL) was added Pd / C (250 mg) at room temperature. The reaction mixture was stirred overnight under H2 (2 atm). The suspension was filtered and the filtrate was concentrated to afford the crude product step 4 product (3.88 g, 100 %) which was used in next step without further purification. MS m / z [M+H]+(ESI):239.12.

[0891] Step 5

[0892] To a solution of step 4 product (3.88 g, 13.3 mmol, 1.0 equiv) in trifluoroacetic acid (10 mL) was added TFAA (8.5 mL, 66.6 mmol, 5.0 equiv) at room temperature and the reaction mixture was stirred overnight. The reaction was diluted with EtOAc and washed with water (25 mL), brine (25 mL), dried over Na2SO4, filtered and concentrated to give a crude productPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 which was purified by silica gel chromatography (petroleum ether: ethyl acetate = 5 : 1) to afford the step 5 product (1.2 g, 56%) as a colorless oil. MS m / z [M+H]+(ESI):221.11.

[0893] Step 6

[0894] To a solution of step 5 product(1.2 g, 5.45 mmol, 1.0 equiv) in te / T-Butanol / diethyl ether (10 mL / 10 mL) was added potassium Zc / V-butoxide (911 mg, 8.12 mmol, 1.5 equiv) and tert-butyl nitrite (843 mg, 8.12 mmol, 1.5 equiv) at room temperature and the reaction mixture was stirred overnight. The reaction was quenched with water (25 mL), adjusted to pH=2 with aqueous hydrochloric acid and extracted with dichloromethane (30 mL x 3). The combined organic extracts were washed with water (25 mL), brine (25 mL), dried over Na2SO4, filtered and concentrated to give a crude product which was purified by silica gel chromatography (dichloromethane : methanol = 100: 1) to afford the Step 6 product (700 mg, 51 %) as a yellow solid. MS m / z [M+H]+(ESI):250.10.

[0895] Step 7

[0896] To a solution of step 6 product (500 mg, 2.27 mmol, 1 equiv) in acetic acid (6 mL) was added zinc (445mg, 6.81 mmol, 3.0 equiv) and acetic anhydride (4 mL) at room temperature under N2, and the reaction mixture was stirred overnight. The suspension was filtered, the filtrate diluted with water, adjusted to pH=8 with sodium hydroxide (4 M in water) and extracted with ethyl acetate. The extract was washed with water (25 mL), brine (25 mL), dried over Na2SO4, filtered and concentrated to give a crude product which was purified by silica gel chromatography (di chloromethane: methanol= 100: 1) to afford the step product 7 (180 mg, 40%) as a colorless oil. MS m / z [M+H]+(ESI):250.10.

[0897] Step 8

[0898] To a solution of step 7 product (184 mg, 0.664 mmol, 1.0 equiv) in methanol (10 mL) was added Sodium borohydride (76 mg, 2.0 mmol, 3.0 equiv) at 0°C. The reaction mixture was stirred at room temperature overnight. The reaction was diluted with ethyl acetate, washed with water (25 mL), brine (25 mL), dried over Na2SO4, filtered and concentrated to give the crude product Step 8 product (203 mg, 100%) which was used in next step without further purification. MS m / z [M+H]+(ESI):280.15.

[0899] Step 9

[0900] To a solution of step 8 product (158 mg, 0.565 mmol, 1 equiv) in water (5 mL) was added concentrated hydrochloric acid (12 M in water, 0.8 mL) at room temperature. The reaction mixture was stirred at reflux for 2 h, cooled to room temperature and adjusted to pH = 8 with sodium hydroxide (4 M in water). The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water (25 mL), brine (25 mL), dried over Na2SO4, filteredPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 and concentrated to give the crude product step 9 product (143 mg, 56%) which was used in next step without further purification. MS m / z [M+H]+(ESI):238.14

[0901] Step 10

[0902] To a solution of step 9 product (80 mg, 0.33 mmol, 1 equiv) in trifluoroacetic acid (6mL) was added EtsSiH (206 mg, 1.65 mmol, 5 equiv) at room temperature and the reaction mixture was stirred overnight. The reaction was diluted with water (25 mL), adjust to pH=10 with sodium hydroxide (4 M in water). The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, brine (25 mL each) and dried over Na2SC>4, filtered and concentrated to give a crude product which was purified by silica gel chromatography (dichloromethane: methanol = 100: 1) to afford the 31 as a colorless oil (64 mg, 86%). MS m / z [M+H]+(ESI):222.14.

[0903] Compound 3, 4, 5 and 11 were also prepared by alternative methods and descrived as follows.

[0904] General synthesis Scheme 1.1PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0905] Stepl

[0906] To a stirred mixture of 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-one (70 g,339.409 mmol, 1 equiv) and (R)-2-methylpropane-2-sulfinamide (65.82 g, 543.054 mmol, 1.6 equiv) in THF (1400 mL) were added Ti(OEt)4 (131.62 g, 576.995 mmol, 1.7 equiv) in portions at 20 °C under nitrogen atmosphere. The resulting mixture was stirred at 60 °C for 2 h under nitrogen atmosphere. The reaction was quenched by the addition of sat. Na2COs (aq.) (1000 mL) at 0 °C. The resulting mixture was filtered, the filter cake was washed with EtOAc (3x200 mL). The resulting mixture was extracted with EtOAc (3 x 1000 mL). The combined organic layers were washed with brine (1x2000 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (2: 1) to afford (R)-N-(5,8-dimethoxy-3,4-PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 dihydro-lH-naphthalen-2-ylidene)-2-methylpropane-2-sulfinamide (85 g) as a yellow solid. ESLMS m / z = 310.1 [M+H]+; Calculated MW:309.1.

[0907] Step 2

[0908] To a stirred mixture of (R)-N-(5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-ylidene)- 2-methylpropane-2-sulfinamide (85 g, 274.708 mmol, 1 equiv) in THF (800 mL) were added NaBTU (41.57 g, 1098.832 mmol, 4 equiv) in portions at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at 20 °C for 16 h under nitrogen atmosphere. The reaction was quenched with sat. NEUCl (aq.) at 0 °C. The resulting mixture was extracted with EtOAc (3 x 1000 mL). The combined organic layers were washed with brine (1x2000 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 100% gradient in 25 min; detector, UV 220 nm. This resulted in (R)-N-(5, 8-dimethoxy-l, 2,3,4- tetrahydronaphthalen-2-yl)-2-methylpropane-2-sulfinamide (58 g) as a brown oil. ESLMS m / z = 312.2 [M+H]+; Calculated MW:311.2.

[0909] Step 3(R)-N-(5, 8-dimethoxy-l, 2, 3, 4-tetrahydronaphthalen-2-yl)-2-methylpropane-2-sulfinamide (40 g, 128.436 mmol, 1 equiv) was purified by Prep SFC, Column: (S, S)-WHELK-O1- Kromasil, 5*25 cm, 10 pm; Mobile Phase A: CO2, Mobile Phase B: IP A: ACN=4: l(20mMNH3); Flow rate: 200 mL / min; Gradient: isocratic 25% B; Column Temperature(°C): 30; Back Pressure(bar): 100; Wave Length: 300 nm; RTl(min): 8.43; RT2(min): 10.05; Sample Solvent: MeOH: DCM=1 : 1— HPLC; Injection Volume: 3 mL; Number Of Runs: 187. This resulted in (R)-N-[(2R)-5, 8-dimethoxy-l, 2,3, 4-tetrahydronaphthalen-2-yl]-2- methylpropane-2-sulfmamide: 1.1C (18 g) (RT1 : 8.43 min)as a brown solid. ESLMS m / z = 312.2 [M+H]+; Calculated MW:311.2.

[0910] This resulted in (R)-N-[(2S)-5, 8-dimethoxy-l, 2,3, 4-tetrahydronaphthalen-2-yl]-2- methylpropane-2-sulfmamide: 1.1D (17 g,) (RT2: 10.05 min) as a brown oil. ESLMS m / z = 312.2 [M+H]+; Calculated

[0911] Step 4

[0912] To a stirred mixture of (R)-N-[(2R)-5, 8-dimethoxy-l, 2,3, 4-tetrahydronaphthalen-2-yl]- 2-methylpropane-2-sulfinamide (18 g, 57.796 mmol, 1 equiv) in HO Ac (300 mL) was added NIS (117.03 g, 520.164 mmol, 9 equiv) in portions at 20 °C under nitrogen atmosphere. The resulting mixture was stirred at 20 °C for 16 h under nitrogen atmosphere. The reaction was quenched with sat. Na2SOs (aq.) at 0 °C The mixture was basified to pH 8 with saturatedPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699NaHCCh. And then to the mixture was added BOC2O (23.58 g, 108.054 mmol, 2 equiv) in portions at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at 20 °C for additional 16 h. The resulting mixture was extracted with EtOAc (3 x 500 mL). The combined organic layers were washed with brine (1x1000 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (12: 1) to afford tert-butyl N-[(2R)-6- iodo-5,8-dimethoxy-l,2,3,4-tetrahydronaphthalen-2-yl]carbamate (8 g) as a yellow solid. ESIMS m / z = 378.1 [M-t-Bu+H]+;

[0913] Step 5

[0914] tert-butyl N-[(2R)-6-iodo-5,8-dimethoxy-l,2,3,4-tetrahydronaphthalen-2-yl]carbamate (4 g, 9.232 mmol, 1 equiv) was purified by SFC, Column: CHIRALPAK IG, 3*25 cm, 5 pm; Mobile Phase A: CO2, Mobile Phase B: IPA(0.5% 2M NH3-MeOH)-HPLC; Flow rate: 100 mL / min; Gradient: isocratic 30% B; Column Temperature(°C): 30; Back Pressure(bar): 100; Wave Length: 235 nm; RTl(min): 4.12; RT2(min): 5.2; Sample Solvent: MEOH: DCM=1 : 1; Injection Volume: 1 mL; Number Of Runs: 28. This resulted in tert-butyl N-[(2R)-6-iodo-5,8- dimethoxy-l,2,3,4-tetrahydronaphthalen-2-yl]carbamate: 1.1C2 (1.6 g) (RT1 : 4.12 min) as a yellow solid. ESI-MS m / z = 456.1 [M+Na+H]+; Calculated MW:433.1.This resulted in tertbutyl N-[(2R)-7-iodo-5,8-dimethoxy-l,2,3,4-tetrahydronaphthalen-2-yl]carbamate: 1.1C3 (1.45 g) (RT2: 5.2 min) as a yellow solid. ESLMS m / z = 456.1 [M+Na+H]+; Calculated MW:433.1.

[0915] Step 6

[0916] To a stirred mixture of tert-butyl N-[(2R)-6-iodo-5,8-dimethoxy-l, 2,3,4- tetrahydronaphthalen-2-yl]carbamate (800 mg, 1.846 mmol, 1 equiv) in Dioxane (5 mL) were added HC1 in 1,4-dioxane (4.0 M) (5 mL) in portions at 20 °C under nitrogen atmosphere. The resulting mixture was stirred at 20 °C for 4 h under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. This resulted in (2R)-6-iodo-5,8-dimethoxy-l, 2,3,4- tetrahydronaphthalen-2-amine hydrochloride (615.5 mg, 90.19% yield, 98.0% purity) as a white solid. ESLMS m / z = 334.0 [M+H]+; Calculated MW:333.0.

[0917] 1H NMR (400 MHz, DMSO-d6) 5 8.33 (s, 3H), 7.16 (s, 1H), 3.76 (s, 3H), 3.63 (s, 3H), 3.39 (s, 1H), 3.06 - 2.88 (m, 2H), 2.71 (ddd, J = 17.5, 11.2, 5.6 Hz, 1H), 2.46 (dd, J = 17.0, 9.4 Hz, 1H), 2.10 (d, J = 11.8 Hz, 1H), 1.69 (qd, J = 11.4, 5.3 Hz, 1H).

[0918] Step 7

[0919] To a stirred mixture of tert-butyl N-[(2R)-7-iodo-5,8-dimethoxy-l, 2,3,4- tetrahydronaphthalen-2-yl]carbamate (900 mg, 2.077 mmol, 1 equiv) in Dioxane (5 mL) werePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 added HC1 in 1,4-dioxane (4.0 M) (5 mL) in portions at 20 °C under nitrogen atmosphere. The resulting mixture was stirred at 20 °C for 6 h under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. This resulted in (2R)-7-iodo-5,8-dimethoxy-l,2,3,4- tetrahydronaphthalen-2-amine hydrochloride (609.7 mg, 79.41% yield, 98.9% purity) as a white solid. ESI-MS m / z = 334.0 [M+H]+; Calculated MW:333.0.

[0920] 1H NMR (400 MHz, DMSO-d6) 5 8.28 (s, 3H), 7.16 (s, 1H), 3.75 (s, 3H), 3.64 (s, 3H), 3.46 (s, 1H), 3.17 (dd, J = 16.7, 5.0 Hz, 1H), 2.81 - 2.64 (m, 2H), 2.49 (s, 1H), 2.09 (s, 1H), 1.70 (dd, J = 12.0, 5.9 Hz, 1H).

[0921] Step 8

[0922] To a stirred mixture of (R)-N-[(2S)-5,8-dimethoxy-l,2,3,4-tetrahydronaphthalen-2-yl]- 2-methylpropane-2-sulfinamide (17 g, 54.585 mmol, 1 equiv) in HOAc (300 mL) was added NIS (110.53 g, 491.265 mmol, 9 equiv) in portions at 20 °C under nitrogen atmosphere. The resulting mixture was stirred at 20 °C for 16 h under nitrogen atmosphere. The reaction was quenched with sat. Na2SOs (aq.) at 0 °C The mixture was basified to pH 8 with saturated NaHCCh. And then to the mixture was added BOC2O (23.58 g, 108.054 mmol, 2 equiv) in portions at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at 20 °C for additional 16 h. The resulting mixture was extracted with EtOAc (3 x 500 mL). The combined organic layers were washed with brine (1x1000 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (12: 1) to afford tert-butyl N-[(2S)-6- iodo-5,8-dimethoxy-l,2,3,4-tetrahydronaphthalen-2-yl]carbamate (6.3 g,) as a yellow solid. ESI-MS m / z = 456.2 [M+Na+H]+; Calculated MW:433.1.

[0923] Step 9

[0924] tert-butyl N-[(2S)-6-iodo-5,8-dimethoxy-l,2,3,4-tetrahydronaphthalen-2-yl]carbamate (4 g, 9.232 mmol, 1 equiv) was purified by SFC: Column: CHIRAL ART Cellulose-SC, 5*25 cm, 10 pm; Mobile Phase A: CO2, Mobile Phase B: MEOH; Flow rate: 200 mL / min; Gradient: isocratic 35% B; Column Temperature(°C): 35; Back Pressure(bar): 100; Wave Length: 220 nm; RTl(min): 3.48; RT2(min): 4.18; Sample Solvent: IPA(20mMNH3); Injection Volume: 1.5 mL; Number Of Runs: 41. This resulted in tert-butyl N-[(2S)-6-iodo-5,8-dimethoxy- l,2,3,4-tetrahydronaphthalen-2-yl]carbamate: 1.1D1 (1.35 g,) (RT1 : 3.48 min) as a yellow solid. ESI-MS m / z = 456.1 [M+Na+H]+; Calculated MW:433.1.This resulted in tert-butyl N- [(2S)-7-iodo-5,8-dimethoxy-l,2,3,4-tetrahydronaphthalen-2-yl]carbamate: 1.1D2 (1.7 g,) (RT2: 4.18 min) as a yellow solid. ESI-MS m / z = 456.1 [M+Na+H]+; Calculated MW:433.1.

[0925] Step 10PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0926] To a stirred mixture of tert-butyl N-[(2S)-6-iodo-5,8-dimethoxy-l,2,3,4- tetrahydronaphthalen-2-yl]carbamate (900 mg, 2.077 mmol, 1 equiv) in Dioxane (5 mL) were added HC1 in 1,4-dioxane (4.0 M) (5 mL) in portions at 20 °C under nitrogen atmosphere. The resulting mixture was stirred at 20 °C for 4 h under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. This resulted in (2S)-6-iodo-5,8-dimethoxy-l, 2,3,4- tetrahydronaphthalen-2-amine hydrochloride (617.0 mg) as a white solid. ESI-MS m / z = 334.0 [M+H]+; Calculated MW:333.0.

[0927] 1H NMR (400 MHz, DMSO-d6) 5 8.33 (s, 3H), 7.16 (s, 1H), 3.77 (s, 3H), 3.63 (s, 3H), 3.38 (s, 1H), 3.01 (dd, J = 17.2, 5.5 Hz, 1H), 2.93 (dt, J = 17.5, 4.6 Hz, 1H), 2.71 (ddd, J = 16.9, 10.8, 5.5 Hz, 1H), 2.49 - 2.40 (m, 1H), 2.10 (d, J = 12.5 Hz, 1H), 1.69 (qd, J = 11.3, 5.3 Hz, 1H).

[0928] Step 11

[0929] To a stirred mixture of tert-butyl N-[(2S)-7-iodo-5,8-dimethoxy-l, 2,3,4- tetrahydronaphthalen-2-yl]carbamate (900 mg, 2.077 mmol, 1 equiv) in Dioxane (5 mL) were added HC1 in 1,4-dioxane (4.0 M) (5 mL) in portions at 20 °C under nitrogen atmosphere. The resulting mixture was stirred at 20 °C for 6 h under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. This resulted in (2S)-7-iodo-5,8-dimethoxy-l, 2,3,4- tetrahydronaphthalen-2-amine hydrochloride (609.3 mg,) as a yellow solid. ESI-MS m / z = 334.0 [M+H]+; Calculated MW:333.0.

[0930] 1HNMR (400 MHz, DMSO-d6) 5 8.24 (s, 3H), 7.17 (s, 1H), 3.75 (s, 3H), 3.64 (s, 3H), 3.34 (s, 1H), 3.17 (dd, J = 16.9, 5.0 Hz, 1H), 2.82 - 2.63 (m, 2H), 2.46 (d, J = 9.0 Hz, 1H), 2.10 (d, J = 12.7 Hz, 1H), 1.69 (qd, J = 11.2, 5.8 Hz, 1H).

[0931] Preparation of 187 and 188

[0932] Step 1

[0933] A solution of 5,8-dimethoxy-3,4-dihydro-lH-naphthalen-2-one (500 mg, 2.42 mmol, 1 equiv) in AcOH (5 mL) was added 1 M HNO3 in acetic acid (0.266 mL, 2.66 mmol, 1.1 equiv) at 0-5°C. Then the reaction was stirred at room temperature for 30 min. The reaction was quenched with water (30 mL). The precipitate was collected and washed with water (3^ 10 mL), then dried in high vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, MeCN in waterPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699(lOmmol / L NH4HCO3), 10% to 100% gradient in 20 min; detector, UV 220 nm. This resulted in Crude compound (300 mg, 49% yield) as a brown solid was used next step as such.

[0934] Step 2

[0935] To a solution of crude product from step 1 (100 mg, 0.40 mmol, 1 equiv) in methanol (3 mL) was added ammonium acetate (307 mg, 4.00 mmol, 10 equiv) and sodium bis(acetyloxy)boranuidyl acetate (844 mg, 4.00 mmol, 10 equiv). The mixture was stirred for 16 hours. After concentration, the residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, acetonitrile in water (0.1% NH3.H2O+10mmol / LNH4HCO3), 10% to 100% gradient in 15 min; detector, UV 210 nm. This resulted in crude product. The residue was purified by reversed- phase flash chromatography with the following conditions: Column: XSelect Prep Cl 8 OBD Column 19*250 mm, 5pm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: MeOH; Flow rate: 25 mL / min mL / min; Gradient: 15% B to 26% B in 12 min; Wave Length: 254nm / 220nm nm; RTl(min): 9.27 / 10.35. This resulted in 187 (7.7 mg, 13% yield) as a white solid. MS m / z [M+H]+(ESI):253.05. 'H NMR (300 MHz, Methanol^) 8 8.53 (s, 1H), 7.30 (s, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.60-3.45 (m, 1H), 3.27-3.07 (m, 2H), 2.90-2.79 (m, 1H), 2.64-2.55 (m, 1H), 2.33-2.17 (m, 1H), 1.91-1.73 (m, 1H).

[0936] 188 (8.2 mg, 14% yield) as a white solid. MS m / z [M+H]+(ESI):252.95. 'H NMR (300 MHz, Methanol-A) 5 8.53 (s, 1H), 7.30 (s, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.60-3.45 (m, 1H), 3.38-3.33 (m, 1H), 3.07-2.93 (m, 1H), 2.81-2.63 (m, 2H), 2.33-2.17 (m, 1H), 1.84-1.73 (m, 1H).

[0937] Wherein the variables are as described elsewhere in the present disclosure.

[0938]

[0939] Example 2: Biological Experiments

[0940] Compounds 31, 189, 190, 45, and 126 were assessed for biological activity across a panel of 5-HT receptors including 5-HT2A, 5-HT2B, 5-HT2C and 5-HT1 A. Biased signaling was assessed by monitoring both intracellular Gq-mediated calcium release, as well as betaarrestin activation and recruitment to the GPCR. Tables A and B summarize the findings across these compounds and the 5-HT receptors tested

[0941] Table A. EC50 values measured for Compounds 31 and 189 across a panel of 5-HT receptors.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0942] The 2-aminotetralins studied displayed greater potency for the 5-HT2C receptor compared to the other 5-HT receptors studied (Table A). The 2-aminotetralins studied afforded sub -micromol ar potencies for 5HT1A. In comparison to psilocin (ECso=2,O53nM), 2- aminotetralins were ~5-fold more potent for 5-HT1A. Given the importance of the 5-HT1A contribution to the psychedelic experience (Pokorny et al., 2016; Carter et al., 2005), 5-HT1 A activation afforded by 2-aminotetralins may be therapeutically advantageous.

[0943] While the 2-aminotetralins studied were potent activators of 5-HT2A Gq-mediated signaling, these compounds were found to be less potent activators of beta-arrestin recruitment at 5-HT2A (FIG. 2). Compound 189 was observed to maintain a 14-fold signaling bias compared to ~ 10-fold for Compound 31. Such a signaling bias may be important to uncoupling the psychedelic experiences of disassociation and hallucination from the therapeutic benefit.

[0944] The ECso profiles of the compounds demonstrated that all were agonists of 5-HT2A mediated signaling. However, Compound 31 displayed higher efficacy full agonism of 5- HT2A Gq-mediated signaling (97% max activation) compared to Compound 189 (82% max activation) (FIG. 1) when compared to the maximum reference agonist response (100%). Both compounds showed increased potency and efficacy at 5-HT2A relative to 5-HT2B receptor Gq-mediated signaling (FIG. 1). Compound 31 exhibited higher efficacy partial agonism of 5- HT2A P-arrestin signaling compared to Compound 189 with maximum effect levels of 66% and 35%, respectively.

[0945] Example 3: GPCR Agonism Studies

[0946] In vitro screening was conducted using human 5-HT2A and 5-HT2B receptor IPOne accumulation assays, human 5-HT2A receptor beta-arrestin2 recruitment assay, human 5- HT2C receptor calcium mobilization assay and human 5-HT1A, 5-HT1B, mGluR2 / 3 receptor cAMP assays. Compounds were tested at several concentrations in duplicate in each assay for agonist activity. Nonlinear regression was applied to the concentration-response data toPCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699 estimate EC50 values. Agonist activity was expressed as a percentage of the activity of the reference agonist at its EC 100.

[0947] Human 5-HT2A & 5-HT2B receptor IPOne accumulation HTRF assay data for Compound 189 and Compound 190 are shown in Table B and FIG. 3 A and FIG. 3B, respectively, along with reference compounds, psilocin and lisuride.

[0948] Compound 189 displayed similar agonist potency and efficacy at 5-HT2A and 5-HT2B receptors, while Compound 190 showed increased potency and efficacy at 5-HT2A relative to 5-HT2B receptors (Table B, FIG. 3 A & B).

[0949] Compounds 189 and 190 exhibited increased agonist selectivity for 5-HT2A over 5- HT2B receptors relative to the profile of the reference agonist a-Me-5-HT for which selectivity = 1 (Table B, FIG. 3C).

[0950] Additional human 5-HT2A, 5-HT2C, 5-HT1A, 5-HT1B and mGluR2 / 3 receptor assay data for Compound 189 and Compound 190 are shown in Table B.

[0951] Probability of CNS drug-like properties is shown in FIG. 3D.

[0952] TableB. Agonist potency and efficacy of Compound 189, Compound 190 and reference compounds at multiple 5-HT and glutamate GPCRs.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0953] Example 4: Brain Penetration

[0954] FIG. 4 shows brain plasma exposures of Compounds 189 and 190 following administration to male C57BL / 6 mice and SD rats.

[0955] Example 5: Head Twitch Response

[0956] Head twitch response (HTR) is a behavioral proxy for human hallucinogenic effects (FIG. 5A). To investigate hallucinogenic potential, male C57BL / 6 mice, each implanted with a cranium-attached magnet, were administered compounds of the present disclosure, placed individually in a glass cylinder surrounded by a magnetometer, and the HTR was measured for 30 min.

[0957] The HTR responses were measured for psilocin (FIG. 5B), Compound 189 (FIG. 5C), and Compound 190 (FIG. 5D). Compoud pretreatment (60 min) reduced HTR induced by a known hallucinogen, DOI, in a dose-dependent manner (FIG. 5E, F). These data are indicative of 5-HT2A receptor interactions in vivo.

[0958] Example 6: Forced Swim Testing

[0959] Antidepressant-like properties of compounds of the present disclosure were measured in the Forced Swim Test (FIG. 6A). Male C57BL / 6 mice were injected with test compounds and 24h later placed individually in a cylinder of water, where immobility was analyzed for 4 min. The data for Compound 189 is shown at FIG. 6B (up to 10 mg / kg), Compound 190 is shown at FIG. 6C (up to 30 mg / kg) and psilocybin is shown in both FIG. 6B & C (5 mg / kg).

[0960] Example 7: Translational Antidepressant-Like Effects

[0961] Translational antidepressant potential was tested in male Wistar Kyoto rats, which exhibit depression-like phenotypes, including increased rapid eye movement (REM) sleep. REM sleep was measured by EEG and EMG electrodes for 6 hours following administration of compounds.

[0962] The effects of Compounds 189 and 190 on REM sleep are shown in FIGs. 7C and 7E (10 mg / kg), respectively, and for psilocybin (FIG. 7A, 10 mg / kg). The effects on REM sleep latency are shown in FIG. 7D (Compound 189), FIG. 7F (Compound 190, p = 0.01) and FIG. 7B (psilocybin).

[0963] Example 8. Activity Data

[0964] Table C. Functional Agonist Activity Data for Select Compounds of the Present DisclosurePCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0965] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.

[0966] While the invention has been described in connection with proposed specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth and as follows in the scope of the appended claims.PCT / US25 / 44749 03 September 2025 (03.09.2025)Atorney Docket No.: ATAI-115 / 01WO 338067-2699

[0967] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.

[0968] While the invention has been described in connection with proposed specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth and as follows in the scope of the appended claims.

Claims

Attorney Docket No.: ATAI-115 / 01WO 338067-2699CLAIMS1. A compound of Formula (V):or a pharmaceutically acceptable salt thereof, wherein: Rs, R9, and Rio are each independently -H or -alkyl;(1) R11 and R12 are each independently -H, -alkyl, -alkylene-OH, -alkylene-O-alkyl, - alkylene-C(O)-OH, -alkylene-C(O)-O-alkyl, -alkylene-O-C(O)-alkyl, -C(NRi3)-N(Ri3)2, or - C(NRi3)-N(Ri3)2;(2) R11 and R12 together with the nitrogen to which they are attached form a - heterocyclyl or -heteroaryl; or(3) R11 is -aryl, -cycloalkyl, -heterocyclyl, heteroaryl, -alkylene-aryl, -alkylenecycloalkyl, -alkylene-heterocyclyl, or -alkyene-heteroaryl, and R12 is -H, -alkyl, -alkylene- OH, -alkylene-O-alkyl, -alkylene-C(O)-OH, -alkylene-C(O)-O-alkyl, -alkylene-O-C(O)- alkyl, -C(NRi3)-N(Ri3)2, or -C(NRi3)-N(Ri3)2;R13 is -H or -alkyl; m is 0 or 1; n is 1, 2 or 3; and p is 1 or 2;Attorney Docket No.: ATAI-115 / 01WO 338067-26992. The compound of claim 1, wherein Rs, R9, and Rio are -H.

3. The compound of claim 1, wherein Rs, R9, and Rio are -alkyl.

4. The compound of claim 1, wherein Rs, R9, and Rio are -methyl.

5. The compound of claim 1, wherein R11 and R12 are each independently -H or -alkyl.

6. The compound of claim 1, wherein one of R11 and R12 is -H and one of R11 and R12 is -alkyl.

7. The compound of claim 1, wherein one of R11 and R12 is -H and one of R11 and R12 is-alkylene-aryl.

8. The compound of claim 1, wherein m is 1.

9. The compound of claim 1, wherein n is 1.

10. The compound of 1, wherein p is 1.

11. The compound of claim 1, having the following formula (V-A)or a pharmaceutically acceptable salt thereof, wherein:Ri, R2, and R? are each independently -H or -alkyl;(1) R4 and Rs are each independently -H or -alkyl; or(2) R4 is -alkylene-aryl and Rs is -H.Attorney Docket No.: ATAI-115 / 01WO 338067-269912. The compound of claim 1, wherein the compound is:or a pharmaceutically acceptable salt thereof, wherein:R13 and Ri4 are each independently -H or -alkyl;Ris and Ri6 are each independently -H, -halo, -S(O)2Ri7, -alkyl, -cycloalkyl, - haloalkyl, -CN, -ORis, -SRis, -heteroalkyl, -heteroaryl, or -heterocyclyl;R17 is -alkyl or -haloalkyl;Ris is -H, alkyl, or -haloalky; andRing A is -heterocyclyl,Attorney Docket No.: ATAI-115 / 01WO 338067-269915. The compound of claim 14, wherein R13 and R14 are -alkyl.

16. The compound of claim 14, wherein R15 and Ri6 are independently -H, -halo, - S(O)2Ri7, -haloalkyl, -alkyl, or cycloalkyl.

17. The compound of claim 14, wherein Ring A is:wherein: q is 0, 1, 2, or 3; andR19 is -H, -OH, -O-alkyl, -NH2, -NH(alkyl), -N(alkyl)2, -heterocyclyl, -aryl, or heteroaryl.

18. The compound of claim 17, wherein q is 1.Attorney Docket No.: ATAI-115 / 01WO 338067-269919. The compound of claim 14, wherein Ring A is, wherein Ring B is an -aryl or -heteroaryl.

20. The compound of claim 1, wherein Ring A is:

21. The compound of claim 14, wherein Ring A is:

22. The compound of claim 14, wherein Ring A is a 4 to 5 member -heterocyclyl.

23. The compound of claim 14, wherein the compound is:Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-269924. The compound of claim 14, wherein the compound is:Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Attorney Docket No.: ATAI-115 / 01WO 338067-269925. A compound of formula (VII):or a pharmaceutically acceptable salt thereof, wherein:R20 and R21 are each independently -H or -alkyl;Attorney Docket No.: ATAI-115 / 01WO 338067-2699R22 and R23 are each independently -H, -halo, -S(O)2R26, -alkyl, -cycloalkyl, - haloalkyl, -CN, -OR27, -SR27, -heteroalkyl, -heteroaryl, -alkylene-O-alkyl, or -heterocyclyl; andR24 and R25 are each independently -H, -alkylene-heterocyclyl, -heterocyclyl, - alkylene-aryl, -aryl, -alkylene-heteroaryl, or -heteroaryl, wherein one of R24 and R25 is -alkylene-heterocyclyl, -heterocyclyl, -alkylene-aryl, - aryl, -alkylene-heteroaryl, or -heteroaryl;R26 is -alkyl or -haloalkyl; andR27is -H, alkyl, or -haloalky,Atorney Docket No.: ATAI-115 / 01WO 338067-2699Attorney Docket No.: ATAI-115 / 01WO 338067-269926. The compound of claim 25, wherein R20 and R21 are -alkyl.

27. The compound of claim 25, wherein R22 and R23 are each independently -H, -CN, or - halo.

28. The compound of claim 25, wherein one of R24 and R25 is -H and one of R24 and R25 is -alkylene-heterocyclyl, -heterocyclyl, -alkylene-aryl, -aryl, -alkylene-heteroaryl, or - heteroaryl.

29. The compound of claim 25, wherein one of R24 and R25 is -alkylene-aryl, -aryl, - alkylene-heteroaryl, or -heteroaryl.Atorney Docket No.: ATAI-115 / 01WO 338067-269930. The compound of claim 25, wherein one of R24 and R25 is -alkyl ene-aryl, -aryl, - alkylene-heteroaryl, or -heteroaryl.

31. The compound of claim 25, wherein one of R24 and R25 iswherein: r is 1 or 2; andR28 is -O-alkyl, -OH, or -alkyl.

32. The compound of claim 25, wherein one of R24 and R25 is33. The compound of claim 25, wherein the compound is:Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-269934. The compound of claim 25, wherein the compound is:Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Attorney Docket No.: ATAI-115 / 01WO 338067-269935. A compound of F ormula (VIII) :or a pharmaceutically acceptable salt thereof, wherein:R28 and R29 are each independently -H or -alkyl;R30 and R31 are each independently -H, branched -alkyl, -haloalkyl, -alkylene-S(O)2-R32, -alkylene-O-R33, -alkylene-(O)-OR33, or -alkylene-O-R32; wherein at least one of R30 and R31 is not -H;R.32 is -alkyl or -haloalkyl;R33 is -H, -alkyl, or -haloalkyl; wherein the compound is not:Attorney Docket No.: ATAI-115 / 01WO 338067-269936. The compound of claim 35, wherein R28 and R29 are -alkyl.

37. The compound of claim 35, wherein R30 and R31 are each independently -haloalkyl, - alkylene-S(O)2-R32, -alkylene-O-R33, -alkylene-(O)-OR33, or -alkylene-O-R33.

38. The compound of claim 35, having the following formula (VIII-A):or a pharmaceutically acceptable salt thereof, wherein:R28 and R29 are each independently -H or -alkyl;R34 is -O-alkyl, -C(O)-OH, -S(O)2-alkyl, -OH, -O-alkyl, or -O-haloalkyl.Attorney Docket No.: ATAI-115 / 01WO 338067-269940. A compound of Formula (IX)or a pharmaceutically acceptable salt thereof, wherein:R35 and R36 are -alkyl;R37 and R38 are each independently -H, -halo, -S(O)2R4i, -S(O)(NH), -alkylene, -alkyl, -cycloalkyl, -haloalkyl, -CN, -OR42, -SR42, -heteroalkyl, -heteroaryl, -heterocyclyl, -O-alkyl, - O-alkylene-aryl, -aryl, -O-haloalkyl, -NH2, -alkylene -cycloalkyl, -alkylene-OH, or -NO2; wherein at least one of R37 and R38 is not -H;R39 and R40 are each independently -H, -haloalkyl, -alkylene-O-alkyl, -C(=NH)-NH2, or -alkyl;R41 is -alkyl or -haloalkyl; andR42 is -H, -alkyl, or haloalkyl;Atorney Docket No.: ATAI-115 / 01WO 338067-2699Attorney Docket No.: ATAI-115 / 01WO 338067-269941. The compound of claim 40, wherein R35 and R36 are -methyl.

42. The compound of claim 40, wherein R37 and R38 are each independently -halo, -CF3, -S(O)2-Me, -CH2-CH-(CH3)2, -CH2-CH3, -CH-(CH3)2, -cyclopropyl, -S(O)2-CF3, -S(O)(NH), -O-methyl, -CH2CH2CH2CF3, -CH2CH2CH2CH3, -CH2CH2CH2CHF2, -CH2CH2CH2CH2F, - cyclopentyl, -O-CF3, O-CHF2, -NH2, -CH2CH2CH2CH2-OH, -CH2-CH(OH)-CH2-CH3, or - NO2.

43. The compound of claim 40, wherein R39 and R40 are -H.

44. The compound of claim 40, wherein R39 and R40 are each independently -H and - alkyl.Attorney Docket No.: ATAI-115 / 01WO 338067-269945. The compound of claim 40, wherein R39 and R40 are each independently -H and - haloalkyl.

46. The compound of claim 40, wherein the compound is:Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-269946. The compound of claim 40, wherein the compound is:Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-2699Atorney Docket No.: ATAI-115 / 01WO 338067-269947. A compound selected from the group consisting of:Atorney Docket No.: ATAI-115 / 01WO 338067-269948. A compound selected from the group consisting of:Atorney Docket No.: ATAI-115 / 01WO 338067-2699Attorney Docket No.: ATAI-115 / 01WO 338067-269949. A pharmaceutical composition comprising the compound of any one of claims 1-48 and a pharmaceutically acceptable excipient.

50. A method of treating a mental health disease or disorder, the method comprising administering a therapeutically effective amount of a compound of any one of claims 1-48 or the pharmaceutical composition of claim 49.

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