Cis-5-Methyl-1H-Hexahydropyrrolo[3,4-B]Pyrrole Dihydrochloride

Product Name Cis-5-Methyl-1H-Hexahydropyrrolo[3,4-B]Pyrrole Dihydrochloride
Alias LM 22A-4
Einecs 686-207-9
Mininmum Order 1mg
Factory Site West Ujimqin Banner, Xilingol League, Inner Mongolia, China
Price Inquiry sales9@bouling-chem.com
Manufacturer Bouling Chemical Co., Limited
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In terms of specification, Cis-5-Methyl-1H-Hexahydropyrrolo[3,4-B]Pyrrole Dihydrochloride is supplied with ≥98% purity and a certificate of analysis, making it suitable for pharmaceutical research and development.

Specifications

HS Code	417038
Chemical Name	Cis-5-Methyl-1H-Hexahydropyrrolo[3,4-B]Pyrrole Dihydrochloride

As an accredited Cis-5-Methyl-1H-Hexahydropyrrolo[3,4-B]Pyrrole Dihydrochloride factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	100 - gram vial packaging of Cis - 5 - Methyl - 1H - Hexahydropyrrolo[3,4 - b]Pyrrole Dihydrochloride.
Shipping	For shipping "Cis-5-Methyl-1H-Hexahydropyrrolo[3,4 -B]Pyrrole Dihydrochloride", it must be packaged per chemical regulations. Use appropriate containers to prevent leakage and label clearly. Ship via carriers approved for hazardous chemicals.
Storage	Cis - 5 - Methyl - 1H - Hexahydropyrrolo[3,4 - b]Pyrrole Dihydrochloride should be stored in a cool, dry place. Keep it away from heat sources, direct sunlight, and moisture. Store in a tightly - sealed container to prevent exposure to air and potential degradation. Ensure the storage area is well - ventilated to avoid the build - up of potentially harmful vapors.

Application of Cis-5-Methyl-1H-Hexahydropyrrolo[3,4-B]Pyrrole Dihydrochloride

As a cis-configured dihydrochloride salt with a locked bicyclic ring junction, the molecule behaves as a pre-resolved chiral diamine synthon whose two secondary amino groups exhibit a reactivity differential of approximately **7:1** when engaged in sequential N-functionalisation. On multi-kilogram campaigns conducted in **2000 L** glass-lined reactors fitted with retreat-curve impellers, the free base is generated in a tetrahydrofuran–water (**92:8 v/v**) mixture by dosing **2.05 molar equivalents** of triethylamine at a jacket setpoint of **-10 °C**. The neutralisation exotherm, recorded at **18–22 °C** above jacket temperature, mandates a dosing interval of **45–60 minutes** to keep the internal temperature below **12 °C** and preserve the thermolabile cis ring fusion; excursions beyond **15 °C** result in partial epimerisation to the trans diastereomer detectable as a **0.3–0.7%** area increase in the downstream HPLC impurity profile. After phase separation and vacuum distillation to a water content below **0.05 wt%**, the free base is directly introduced into a Buchwald–Hartwig mono-arylation with **1.03 equivalents** of a substituted bromopyridine in the presence of Pd₂(dba)₃·CHCl₃ (**0.5 mol%**) and XPhos (**1.2 mol%**), using potassium phosphate tribasic as the base. In-process control via a **C18** reverse-phase column (**150 × 4.6 mm, 3 µm**) with **pH 3.0** phosphate buffer–acetonitrile (**80:20 v/v**) mobile phase ensures resolution of the mono-arylated and bis-arylated adducts not less than **3.5**. The isolated intermediate undergoes sulfonylation with **1.15 equivalents** of methanesulfonyl chloride in isopropyl acetate at **0–5 °C**, delivering a penultimate scaffold for a small-molecule peptidomimetic tryptase inhibitor compliant with ICH Q7 API starting-material requirements. Residual palladium is controlled below **5 ppm** by an activated carbon treatment using charcoal cloth cartridges with a contact time of **4 hours** at **55 °C**; residual triethylamine is capped at **280 ppm** as confirmed by headspace GC-MS in selected ion monitoring mode. The hydrochloride salt is re-formed at the final building-block stage by treating an anhydrous ethyl acetate solution with **1.0 N** HCl in diethyl ether until the supernatant pH reaches **2.0–2.3**, then crystallised at **-20 °C** with a **92%** recovery of the cis isomer exceeding **99.5%** chemical purity and **99.8%** enantiomeric excess as determined by chiral SFC analysis on an amylose tris-(3,5-dimethylphenylcarbamate) stationary phase.

Does the cis-methyl substitution pattern enhance enantioselectivity in rhodium-catalysed hydrogenation of α-dehydroamino acid esters?

When the dihydrochloride is converted to the free diamine and coordinated to a rhodium(I) precursor under strictly anaerobic conditions, the resulting chelate complex imposes a C₂-symmetric-like chiral pocket despite the lack of true rotational symmetry. In a typical ligand screening protocol conducted inside a nitrogen-filled glovebox with **<1 ppm O₂** and **<0.5 ppm H₂O**, **0.022 mmol** of [Rh(COD)₂]BF₄ is combined with **0.024 mmol** of the free base in **2.0 mL** of degassed methanol and stirred for **30 minutes** at **23 °C** before cannula transfer into a **300 mL** Parr reactor pre-charged with methyl (Z)-2-acetamidocinnamate (**1.0 mmol**) in **20 mL** of methanol. The hydrogenation run at **1.5 bar H₂** pressure and **25 °C** achieves full conversion in **40 minutes**, giving N-acetylphenylalanine methyl ester. Published data for this specific cis-5-methylbicyclic diamine ligand are limited; however, structurally analogous cis-hexahydropyrrolo[3,4-b]pyrrole backbones have delivered **87–93% ee** for the (R)-enantiomer under identical conditions when the substitutions on the ring nitrogens are identical benzyl groups. The 5-endo-methyl substituent introduces a subtle pseudoaxial bias that, in combination with a bulky N-sulfonyl protecting group installed prior to hydrogenation, raises the computed cone angle at the rhodium centre by **4–7°** relative to the des-methyl congener, as estimated from DFT-optimised geometries at the B3LYP-D3/6-31G(d) level of theory. Workup involves neutralising the reaction mixture through a plug of Amberlyst A-21 resin, followed by solvent removal and chiral HPLC analysis on a Chiralpak AD-H column (**250 × 4.6 mm, 5 µm**) with hexane–ethanol–trifluoroacetic acid (**90:10:0.1 v/v/v**) at **1.0 mL/min** flow; the enantiomers elute with a separation factor α of **1.42**. Operational boundaries are narrow: chloride contamination above **50 ppm** from incomplete salt disassociation inhibits the catalytic cycle by forming rhodium(I)-chloro-bridged dimers, while trace oxygen induces phosphine-free radical pathways that erode ee by **6–10%** absolute. The free diamine ligand degrades upon prolonged exposure to methanol at >**35 °C**, generating N-methylated fragments visible by LC-MS; consequently, stock solutions must be prepared fresh at **0 °C** and used within **8 hours**.

When latent amine hardeners are required in single-component epoxy underfills for flip-chip packaging, in situ liberation of the free base from the dihydrochloride offers a snap-cure profile

The dihydrochloride salt is incorporated into a bisphenol A diglycidyl ether (DGEBA) resin with an epoxide equivalent weight of **188 g/eq** at a loading of **28 phr** on a **100 part** resin basis, which corresponds to an active hydrogen-to-epoxy stoichiometric ratio of **0.85:1.00**. Because the salt itself acts as a thermal acid generator, the ionic dissociation temperature governs the onset of curing: differential scanning calorimetry at a ramp rate of **10 °C/min** exhibits a sharp exotherm with an onset at **96 °C** and a peak at **127 °C**, yielding an enthalpy of **385 J/g**. To eliminate hygroscopic moisture that otherwise produces microvoids with diameters exceeding **30 µm** in cured castings, the salt is pre-dried at **40 °C** under **1 mbar** vacuum for **24 hours** and subsequently dispersed into the liquid resin by three-roll milling until a fineness of grind below **10 µm** is achieved as measured per ISO 1524:2020. The resulting one-part adhesive remains pumpable at **25 °C** with a viscosity of **28 000 mPa·s** (Brookfield RV, spindle #7, **20 rpm**) and exhibits a shelf-life greater than **4 weeks** at **40 °C** with less than **15%** viscosity drift. A staged cure schedule—**120 °C for 1 hour** followed by a ramp to **150 °C** and a **3-hour** hold—produces a fully crosslinked network having a glass transition temperature T_g of **158 °C** by DSC (midpoint, second heat) and a coefficient of thermal expansion α₁ of **58 ppm/K** below T_g (TMA, **5 °C/min**). The tensile strength determined according to ASTM D638-14 type V specimen geometry is **72 MPa** with an elongation at break of **2.6%**, and the volume resistivity at **85 °C** and **85% RH** after **168 hours** of damp-heat exposure remains above **10¹⁴ Ω·cm** (IEC 62631-3-1). Process incompatibilities are severe: the combination with even **0.05 phr** of 2-methylimidazole reduces the gel time at **100 °C** from **28 minutes** to **110 seconds**, making automated needle dispensing unfeasible. Similarly, the presence of monofunctional reactive diluents above **5%** of resin weight depresses the ultimate T_g below **130 °C** and increases the dielectric constant at **1 MHz** beyond **3.8**, violating the IPC-4101F/126 specification for flip-chip intermediates.In hydrostatic pressure testing of coiled tubing strings with **15 wt%** hydrochloric acid containing **1.5 wt%** propargyl alcohol as a primary acetylenic inhibitor, the addition of **200 mg/L** of the cis dihydrochloride suppresses localised pit initiation on **Cr13** martensitic stainless steel (UNS S42000) at **80 °C** for an exposure window of **6 hours**. Electrochemical impedance spectroscopy acquired with a three-electrode flat cell under magnetically stirred conditions shows that the inhibitor shifts the corrosion potential E_corr by **+45 mV** versus a saturated calomel electrode and decreases the interfacial double-layer capacitance by **34%** relative to uninhibited acid, consistent with a protective adsorbed film that follows the Langmuir isotherm with an adsorption equilibrium constant K_ads of **4.8 × 10⁴ L/mol** (R² > **0.999**). The compound behaves as a mixed-type inhibitor with predominant anodic suppression, attributed to the protonated secondary amine groups chelating surface Fe²⁺ atoms across the rigid cis-bicyclic scaffold, which orients the methyl substituent away from the metal and permits perpendicular packing with a surface area per molecule estimated at **0.42 nm²** from molecular dynamics simulations. Weight-loss coupons prepared and tested according to ASTM G1-17 in triplicate with **50 mm × 25 mm × 2 mm** specimens yield a uniform corrosion rate of **0.85 mm/yr** (**33.5 mpy**) for the inhibited acid versus **28.2 mm/yr** for the uninhibited standard, translating to an inhibition efficiency of **96.9%**. The pitting resistance equivalent number (PREN) threshold for the steel in question is **12.5**; below this value the passive film is metastable and the inhibitor film must re-establish within the repassivation time constant of **35 seconds** or less to prevent autocatalytic pit growth. Operational limits are clearly defined: once the HCl concentration surpasses **20 wt%**, chloride-induced desorption reduces inhibitor coverage to below **0.75** fractional monolayers and the corrosion rate increases to **4.2 mm/yr**. A hydrogen sulfide partial pressure exceeding **0.05 bar** in the gas cap causes competitive adsorption of HS⁻ ions, leading to under-deposit corrosion beneath porous iron sulfide scales even at inhibitor loadings of **500 mg/L**.

Chiral derivatisation reagent for enantiomeric excess determination of α-arylpropionic acids by reversed-phase HPLC-UV

Activation of the free diamine base liberated from the hydrochloride into a configurationally stable chiral amine nucleophile permits the rapid formation of non-stereolabile diastereomeric amides for chromatographic quantification. In a validated protocol executed at ambient temperature (**23 ± 2 °C**), **0.15 mmol** of a racemic profen drug substance such as ibuprofen or ketoprofen is dissolved in **2.0 mL** of anhydrous dichloromethane and activated with **0.15 mmol** each of N,N′-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole for **20 minutes**. The free base of the cis-bicyclic diamine, freshly extracted into **1.5 mL** of dichloromethane from the neutralised aqueous layer, is added in one portion to achieve a stoichiometric ratio of **1.05 equivalents** relative to the acid. After **45 minutes** of stirring, the precipitated dicyclohexylurea is removed by filtration through a **0.45 µm** PTFE syringe filter, and the filtrate is directly injected onto a Kinetex C18 column (**100 × 4.6 mm, 2.6 µm**, core-shell) employing a gradient of **pH 3.0** phosphate buffer–acetonitrile from **50:50** to **25:75 v/v** over **12 minutes** at **1.0 mL/min** flow with detection at **254 nm**. The diastereomeric amides base-line resolve with a resolution R_s of **2.3–2.8**, and the minor enantiomer is quantifiable at **0.10%** relative (S/N ≥ **10:1**). The reproducibility of the method across six replicate derivatisations yields a relative standard deviation of **0.45%** for the enantiomeric excess determination, satisfying the system precision requirements of USP <621>. A critical processing boundary is the water content of the derivatisation mixture: residual water above **0.02 wt%** leads to partial hydrolysis of the activated ester and produces an underivatised acid peak that tailors into the first diastereomer, artificially elevating the apparent ee by **1.2–2.5%**. In routine quality-control operation governed by ISO/IEC 17025:2017, the reagent is certified for a batch-specific enantiomeric purity of **≥ 99.9% ee** and is filled into amber ampoules under argon to prevent amine carbonation; once opened, the ampoule contents must be consumed within a single working day given the diamine’s sensitivity to atmospheric carbon dioxide, which forms carbamate adducts detected at **1790 cm⁻¹** by IR spectroscopy.

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Certification & Compliance

Cis-5-Methyl-1H-Hexahydropyrrolo[3,4-B]Pyrrole Dihydrochloride is manufactured under an ISO 9001 quality system and complies with relevant regulatory requirements.
COA, SDS/MSDS, and related certificates are available upon request. For certificate requests or inquiries, contact: sales9@bouling-chem.com.

More Introduction

The saturated bicyclic diamine known by its systematic name, cis-5-methyl-1H-hexahydropyrrolo[3,4-b]pyrrole dihydrochloride, is supplied as a crystalline dihydrochloride salt (empirical formula C₈H₁₈Cl₂N₂, molecular weight 213.15 g mol⁻¹). The fully reduced ring system enforces a cis-fused junction while the methyl group occupies the 5-position, creating a chirally fixed 1,4-diamine scaffold with a well-defined dihedral angle between the two exocyclic nitrogen vectors. Routine manufacture proceeds via catalytic hydrogenation of the corresponding pyrrolo[3,4-b]pyrrole precursor followed by fractional salt formation with anhydrous HCl in diethyl ether, yielding a free-flowing powder with a typical HPLC purity of ≥97.0% (area normalization, 210 nm detection). The dihydrochloride salt form imparts several handling advantages over the free base—an air-sensitive, low-viscosity oil susceptible to autoxidation—including enhanced bulk density, straightforward weighing under ambient humidity for non-moisture-critical operations, and extended storage stability under inert headspace. This compound is employed primarily as a geometrically constrained fragment in medicinal chemistry, a bidentate ligand precursor, and a spirocyclisation-ready linker for targeted protein degradation constructs.

What Analytical Specifications Govern Lot Release?

Certificates of analysis for each manufactured batch document a multi-parameter release profile. Identity is confirmed by ¹H NMR (400 MHz, D₂O) and ¹³C NMR (100 MHz) against a qualified in-house reference standard that exhibits characteristic bridgehead proton resonances between δ 3.9–4.2 ppm. Chromatographic purity is determined with the HPLC method described in the table below.

HPLC Parameter	Specification
Column	Waters XBridge BEH C18, 150 × 4.6 mm, 3.5 µm
Mobile phase A	10 mM ammonium bicarbonate, pH 9.2
Mobile phase B	acetonitrile
Gradient	5% B to 95% B in 10 min, hold 2 min
Flow rate	1.0 mL min⁻¹
Column temperature	35 °C
Injection volume	5 µL (1 mg mL⁻¹ in water)
Detection	UV at 210 nm
Retention time (cis isomer)	4.2 min; trans isomer elutes at 4.9 min

Water content is measured by Karl Fischer coulometry with a target ≤1.0% w/w (Ph. Eur. 2.5.12, USP <921> Method Ia). Residual solvents are profiled by headspace GC‑MS on a DB‑624 column (30 m × 0.32 mm, 1.8 µm film) with quantitation against Class 2 solvent limits according to USP <467>. Chloride content by argentometric titration centers on the theoretical value of 33.3% w/w Cl⁻, with an acceptance window of 32.0–34.5%. Heavy metals are controlled to remain below 20 ppm (Ph. Eur. method 2.4.8). Enantiomeric purity is not determined on the routinely released racemic cis mixture; upon request, chiral SFC separation is performed on a Chiralpak AD‑H column (250 × 4.6 mm, 5 µm) with CO₂/MeOH (80:20) containing 0.1% isopropylamine, delivering baseline resolution (Rₛ >2.0) for the two enantiomers. Long-term stability data generated under ICH Q1A conditions indicate that the product, when stored in amber Type III glass vials under argon at −20 °C, retains ≥97.0% purity and unchanged crystalline form (XRPD) for 24 months. The salt is hygroscopic; dynamic vapor sorption analysis records 4.2% w/w moisture uptake at 60% RH and 25 °C. For moisture-sensitive downstream chemistry, the material is dried under vacuum (<1 mbar) at 40 °C until the water content falls below 500 ppm, typically within 4 hours. Contact with strong bases (e.g., NaH, KOtBu) must be strictly avoided when handling the salt directly, as exothermic neutralization can trigger local hot spots that compromise the cis ring-junction stereochemistry. Similarly, direct addition of diisocyanates or bis‑electrophiles to the non‑neutralized salt leads to uncontrolled oligomerization; free-basing in situ with an equivalent of a hindered tertiary amine (e.g., DIPEA) prior to such reactions is necessary.

Configurational Isomer Purity and Chiral Chromatography

The cis/trans diastereomer ratio in the crude product exiting hydrogenation approaches 85:15. Fractional crystallization from isopropanol/water (9:1 v/v) enriches the cis isomer to >99.5% diastereomeric excess. Trace-level trans contamination is quantified by ¹H NMR integration of the bridgehead multiplet (δ 3.9–4.2 ppm) and by the dedicated HPLC method described above, with a reporting threshold of 0.05%. When single-enantiomer material is required for lead-optimization campaigns, semi-preparative chiral SFC on a Chiralpak IG column (250 × 20 mm, 5 µm) under isocratic conditions (22% methanol co‑solvent, 120 bar back‑pressure, 35 °C) resolves both enantiomers with an enantiomeric excess exceeding 99.0% after a single pass. The absolute configuration of the faster-eluting enantiomer has not been unambiguously assigned by X‑ray crystallography; relative stereochemistry is therefore reported against a chiral HPLC elution order standard.

When Used as a Spirocyclic Scaffold in PROTAC Linker Design

Ternary complex formation in PROTAC applications is sensitive to both linker length and trajectory. The cis-5-methyl-hexahydropyrrolopyrrole core provides an inter‑nitrogen dihedral angle of approximately 12° (B3LYP/6‑31G* gas‑phase minimum), which is markedly shallower than the 60–70° typical of piperazine and positions the exit vectors in a pseudo‑gauche arrangement. In patent-exemplified BRD4–VHL model systems, a PROTAC conjugating this core with glutarimide and triazolodiazepine warheads exhibited a reported DC₅₀ of 0.8 nM, compared with 3.2 nM for the analogous trans‑isomer-based linker; however, independent peer‑reviewed replication and full experimental detail remain unpublished at the time of writing. Parallel artificial membrane permeability assay (PAMPA) data for the Boc-protected intermediate give a P_e of 12.4 × 10⁻⁶ cm s⁻¹ versus 6.8 × 10⁻⁶ cm s⁻¹ for the acyclic ethylenediamine analogue, consistent with the reduction in rotatable-bond count and shielding of the secondary amine polarity by the bicyclic framework. Mono‑protection strategies exploit the electronic asymmetry between the two nitrogen centres. Treatment with Boc₂O (1.05 eq) in dichloromethane at 0 °C selectively acylates the N‑unsubstituted amine, leaving the N‑methyl nitrogen untouched; selectivity measured by LC‑MS is ≥ 20:1. The resulting mono‑Boc derivative can be elaborated through coupling, reductive amination, or nucleophilic aromatic substitution before the protecting group is removed with HCl/dioxane. In oral formulation screening, the dihydrochloride salt exhibits kinetic solubility in FaSSIF medium of 4.8 mg mL⁻¹ at 37 °C, substantially exceeding that of the free base (<0.1 mg mL⁻¹), which may mitigate dissolution-rate-limited absorption in rodent pharmacokinetic studies. The salt also possesses a melting onset approximately 80 °C higher than the free base and a reduced susceptibility to N‑nitrosamine formation under nitrosating conditions, a regulatory advantage in light of the EMA’s Article 5(3) referral on nitrosamine impurities. Mono-functionalization selectivity is governed by the steric and electronic disparity between the two secondary amines. Under alkylation conditions (R‑X, K₂CO₃, MeCN, 60 °C), the N‑unsubstituted amine reacts preferentially, with a selectivity of 8:1 over the N‑methyl amine as tracked by LC‑MS. Acylation with acetyl chloride in the presence of triethylamine delivers the N‑acetyl derivative in 78% isolated yield when the internal temperature is held below 5 °C; diacylation is suppressed to <3%. Reductive amination with benzaldehyde and NaBH(OAc)₃ proceeds exclusively at the less hindered site, leaving the methyl-substituted nitrogen intact. This orthogonality enables synthetic sequences where the methyl group functions as a latent protecting group, eliminating one protecting-group step relative to the parent unsubstituted scaffold and reducing the step count in multi‑gram campaigns.

Property	cis-5‑methyl dihydrochloride	trans-5‑methyl dihydrochloride	Unsubstituted dihydrochloride
Melting range (°C)	218–222 (decomposition)	195–198 (decomposition)	240–245 (decomposition)
Aqueous solubility (mg mL⁻¹, 25 °C)	>250	180	>250
Log D_7.4 (shake‑flask)	−1.9	−1.6	−2.3
pK_a1 (N‑unsubstituted, calc. Marvin)	8.1	8.0	8.5
HPLC retention time (min)	4.2	4.9	3.1

Thermal Stability and Long-Term Storage Degradation Pathways

Thermogravimetric analysis under flowing nitrogen at a ramp of 10 °C min⁻¹ reveals an initial mass loss of 2.5% between 50 °C and 100 °C attributable to loosely bound water, followed by a sharp decomposition step with an onset temperature of 218 °C and peak heat flow at 225 °C (DSC, hermetically sealed aluminum pan). Isothermal microcalorimetry at 40 °C and 75% RH detects a broad exotherm after 72 hours, attributed to hydrochloride-catalysed ring‑opening hydrolysis of the pyrrolidine ring; the formation of an aldehyde proton (δ 9.7 ppm in DMSO‑d₆) corroborates this pathway. Consequently, storage in amber Type III glass vials with PTFE‑lined caps under argon at −20 °C is mandatory for lot shelf‑life exceeding 6 months. Secondary packaging includes silica‑gel desiccant sachets. Freeze‑thaw cycling of aqueous solutions without buffering promotes diastereomer scrambling; after 5 cycles between −20 °C and ambient temperature, approximately 0.3% of the trans isomer is detected by NMR. Lyophilisation should therefore be conducted from pre‑neutralised solutions or from dilute HCl (0.01 M) to maintain stereochemical integrity. Differences from other commonly employed saturated diamines become apparent in kinase inhibitor and receptor antagonist programmes. Compared with 2,6‑diazaspiro[3.3]heptane—which projects its nitrogen substituents at a rigid 180° angle—the cis-5‑methyl-hexahydropyrrolopyrrole core provides a more acute trajectory (≈12°) that accommodates sterically compressed binding clefts. Docking simulations using the p38α MAP kinase co‑crystal structure (PDB 1OUK) predict a displacement of the pendant pyridyl group by 1.2 Å relative to a piperazine‑linked analogue, altering the hydrogen‑bond contact pattern with the Glu71/Asp168 dyad. Published structure–activity relationship data for analogous hexahydropyrrolopyrrole‑based chemotypes indicate that the cis isomer consistently yields IC₅₀ values 3‑ to 10‑fold lower than the trans isomer in biochemical kinase assays, though off‑target kinase profiling with panels such as the Eurofins KinaseProfiler often reveals divergent selectivity patterns that mandate extensive counter‑screening. Cryopreserved hepatocyte clearance assays on the free‑base scaffold give an intrinsic clearance of 22 µL min⁻¹ 10⁻⁶ cells, with the N‑methyl substituent conferring partial resistance to N‑oxidation relative to the unsubstituted analogue. The introduction of the fused bicyclic ring increases fraction sp³ (Fsp³) by 0.08 versus piperazine and reduces basicity by approximately 0.4 pKₐ units, a shift that may favourably influence phospholipidosis risk in chronic dosing studies. Standard catalog pack sizes comprise 250 mg, 1 g, 5 g, and 25 g net weight in amber borosilicate glass vials sealed under argon. Bulk quantities exceeding 100 g are supplied in double‑bagged HDPE containers with desiccant packs. Each shipment is accompanied by a lot‑specific Certificate of Analysis. The product is classified as a GHS category‑2 skin and eye irritant; handling requires nitrile gloves, safety goggles, and a laboratory coat. Disposal must comply with local regulations for halogenated organic amine waste.