5-Thiazolecarboxaldehyde

Product Name 5-Thiazolecarboxaldehyde
Alias 5-Thiazolecarboxylic aldehyde
Einecs 262-051-3
Mininmum Order 1g
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, 5-Thiazolecarboxaldehyde is supplied with ≥97% purity (GC) and a colorless to pale yellow liquid appearance, making it suitable for use as a pharmaceutical intermediate and heterocyclic building block in research applications.

Specifications

HS Code	397117
Chemical Formula	C4H3NOS
Molar Mass	113.14 g/mol
Appearance	Typically a liquid
Boiling Point	Varies, but around a certain temperature
Melting Point	Specific melting point value
Solubility In Water	Limited solubility
Solubility In Organic Solvents	Soluble in some organic solvents
Density	Certain density value
Odor	May have a characteristic odor
Flash Point	Specific flash point value
Stability	Stable under normal conditions

As an accredited 5-Thiazolecarboxaldehyde factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	100g of 5 - Thiazolecarboxaldehyde packaged in a sealed, chemical - resistant bottle.
Shipping	5 - Thiazolecarboxaldehyde, a chemical, is shipped in well - sealed, corrosion - resistant containers. Shipment follows strict safety protocols for hazardous chemicals, ensuring proper handling and transportation to prevent spills and environmental risks.
Storage	5 - Thiazolecarboxaldehyde should be stored in a cool, dry, well - ventilated area, away from heat sources and open flames. It should be kept in a tightly sealed container to prevent vapor leakage. Due to its potential reactivity, store it separately from oxidizing agents, reducing agents, and strong acids or bases to avoid dangerous reactions. Regularly check storage conditions and container integrity.

Application of 5-Thiazolecarboxaldehyde

In neonicotinoid insecticide supply chains, the conversion of 5-thiazolecarboxaldehyde to 2-chloro-5-chloromethylthiazole remains the highest-volume industrial outlet. This building block is subsequently condensed with N-nitroimino compounds to yield insecticides of the thiamethoxam and clothianidin families. A two-stage sequence is implemented at the 500–2,000 L glass-lined reactor scale. In the first reduction stage, a 25–30°C slurry of 5-thiazolecarboxaldehyde in anhydrous methanol is metered into a vessel containing 1.15 molar equivalents of sodium borohydride suspended in methanol at −5°C to 0°C. The jacket temperature is held by a Lauda or Huber recirculating chiller capable of removing 18–22 kW of exothermic heat. After 2 h post-addition stirring, the batch is quenched with acetone and neutralized to pH 6.5–7.0 with 2N HCl. The resulting 5-hydroxymethylthiazole solution is concentrated in a wiped-film evaporator at 45°C bath temperature and 20 mbar to avoid thermal degradation. Residual water is azeotropically removed with toluene to <0.05 % (w/w) by Karl Fischer titration per ASTM E203-16. The second-stage chlorination is conducted without isolation of the alcohol concentrate. Thionyl chloride (1.3 eq) is dosed via mass flow controller at a rate that keeps the internal temperature between −2°C and +2°C. Off-gases (SO₂, HCl) are scrubbed through a packed column with 10% NaOH solution. After 4 h at 20°C, the batch is distilled under vacuum (90–92°C at 12 mmHg) to deliver 2-chloro-5-chloromethylthiazole in 88–92% yield with gas chromatographic purity ≥99.0%. The material is stabilized with 50 ppm BHT and shipped in 200 L polyethylene drums with PTFE-lined caps under nitrogen. Compliance with REACH regulation requires registration dossiers documenting the absence of mutagenic impurities (ICH M7 Class 2 alkyl chlorides below a calculated limit of 5 µg/day). This intermediate is listed on the active substance inventories of major agrochemical formulators in Brazil, India, and the EU, where regional MRL directives drive meticulous process control documentation for batch traceability.

What controls the residual aldehyde spec in non-nucleoside reverse transcriptase inhibitor intermediates?

Residual free aldehyde in the key intermediate 5-aminomethylthiazole poses a critical quality risk during the manufacture of HIV-1 protease inhibitors containing a thiazol-5-ylmethyl carbamate branching point, such as ritonavir and its lopinavir co-formulation. The reductive amination of 5-thiazolecarboxaldehyde is carried out with 7N ammonia in methanol in the presence of Raney nickel catalyst under 40 bar of hydrogen at 45°C. After filtration through a 0.5 µm sintered metal candle filter to remove catalyst fines, the crude amine solution is assayed for unconverted aldehyde by derivatisation with 2,4-dinitrophenylhydrazine and HPLC-UV at 360 nm. Process robustness studies establish that ammonia stoichiometry below 5 molar equivalents leaves unreacted aldehyde levels above 0.3%, which results in the formation of a dimeric Schiff-base impurity that is difficult to purge during the downstream tert-butyl carbamate protection step. For GMP intermediate release, the specification limits aldehyde content to ≤0.15% (area%) and the palladium content from catalyst leaching to <10 ppm (ICP-MS per ICH Q3D elemental impurity limits for parenteral drug products). The protected amine, 5-(Boc-aminomethyl)thiazole, is isolated by solvent swap from methanol to isopropyl acetate and crystallized at 0°C to achieve a purity of 99.5% with a residual aldehyde value consistently below 80 ppm. Final shipment occurs in double-layered PE bags inside fibre drums with desiccant sachets, accompanied by a certificate of analysis listing USP <467> residual solvent compliance and a nitrosamine risk assessment under EMA/409815/2020.

Condensation with Active Methylene Nucleophiles in Kinase Inhibitor Scaffolds

The Knoevenagel condensation of 5-thiazolecarboxaldehyde with malononitrile or ethyl cyanoacetate serves as a pivotal C–C bond-forming step en route to thiazole-fused pyridine derivatives that inhibit serine-threonine kinases such as CDK7 and PIM1. In a jacketed 160-L glass-lined reactor, equimolar amounts of the aldehyde and malononitrile are dissolved in isopropanol, and 0.05 equivalents of piperidine acetate is added as homogeneous catalyst. The batch is heated to 40–45°C and held for 6 h; product precipitation is monitored by inline turbidity. After cooling to −5°C, the solid is filtered through a centrifuge with a 10 µm polypropylene cloth, washed with chilled isopropanol, and dried in a double-cone vacuum dryer at 40°C and 5 mbar for 8 h. The yield of 2-((thiazol-5-yl)methylene)malononitrile exceeds 94% with an HPLC purity of 99.2%. Residual piperidine is controlled to <50 ppm by ion chromatography on the COA because of its genotoxic alert under ICH M7. When ethyl cyanoacetate is employed, the Knoevenagel adduct requires a subsequent Thorpe-Ziegler cyclisation using 2 eq potassium tert-butoxide in dimethylformamide at 80°C to form the 5-cyanothiazolo[5,4-b]pyridin-4-one core—a scaffold found in ATP-competitive inhibitors. The final active pharmaceutical ingredient is crystallized from acetone/water to reach a polymorphic Form A melting at 238–240°C, a critical quality attribute verified by DSC per ASTM E968-02.

Comparative Performance of 5-Thiazolecarboxaldehyde in Key Downstream Transformations
Transformation / Product Class	Reagent System	Lab Yield	Pilot Scale Yield	Key Equipment / Scale	Critical Purity Control
Reductive alkylation / 5-(Boc-aminomethyl)thiazole	NaBH₄ (1.15 eq) / MeOH; then Boc₂O	92%	88%	500 L glass-lined reactor	Aldehyde <0.15%
Knoevenagel / 2-(Thiazol-5-ylmethylene)malononitrile	Piperidine acetate, i-PrOH	96%	94%	160 L reactor, centrifuge	Piperidine <50 ppm
Pinnick oxidation / 2-Arylthiazole-5-carboxylic acid	NaClO₂, NaH₂PO₄, t-BuOH/H₂O	98%	93%	Hastelloy reactor	Pd <20 ppm
Grignard/oxidation / 2-Acetylthiazole	MeMgCl, then MnO₂	90%	85%	Oldershaw column, 15 theoretical plates	Residual ethanol <0.1%

When a Pinnick Oxidation Delivers Febuxostat-Series Xanthine Oxidase Inhibitors

When the target molecule is a 2-aryl-4-methylthiazole-5-carboxylic acid-class xanthine oxidase inhibitor, such as febuxostat, the aldehyde moiety of 5-thiazolecarboxaldehyde is preserved through a sequence of C2 functionalisation and then oxidised. 5-Thiazolecarboxaldehyde is first subjected to a regioselective lithiation at the −40°C level using lithium 2,2,6,6-tetramethylpiperidide (LiTMP) in anhydrous THF, followed by transmetalation with ZnCl₂ (1.0 eq) and Negishi coupling with an aryl iodide to install the 2-aryl group. After aqueous workup, the crude 2-aryl-5-thiazolecarboxaldehyde is taken into a sodium chlorite oxidation system: a buffered mixture of 1.2 eq NaClO₂, 5 eq NaH₂PO₄, and 2 eq 2-methyl-2-butene as chlorine scavenger in tert-butanol/water at 10°C. The conversion is complete within 3 h; excess oxidant is quenched with sodium sulfite. Acidification to pH 2.0 precipitates the 2-arylthiazole-5-carboxylic acid, which is recrystallized from methanol to give a chromatographic purity above 99.8%. The acid is then coupled with 3-cyano-4-isobutoxyphenylboronic acid via an acyl chloride intermediate to yield febuxostat. For the aldehyde-key intermediate delivered to GMP facilities, the specification mandates a limit of <0.5% des-chloro dimeric impurity and palladium content below 20 ppm per ICH Q3D to meet oral solid dosage form requirements. Commercial packaging in 10-kg LDPE bags within aluminium-laminate pouches minimises photo-degradation of the thiazole ring during transcontinental shipping.

Grignard-based Flavour and Fragrance Thiazole Synthesis

The roast‑aroma compound 2‑acetylthiazole (FEMA 3328, CAS 24295‑03‑2) is obtained from 5-thiazolecarboxaldehyde through a two‑step sequence that avoids direct acetylation of the thiazole nucleus. First, a Grignard addition of methylmagnesium chloride (3.0 M in THF, 1.05 eq) to the aldehyde at −10°C delivers 1-(thiazol-5-yl)ethanol. The reaction is exothermic; the dosing rate is regulated to keep the jacket outlet temperature no higher than 5°C. After quenching with saturated ammonium chloride and phase separation, the intermediate alcohol is oxidised with 2.0 eq of activated MnO₂ in dichloromethane under reflux (40°C) for 4 h. Filtration over Celite and solvent swap to ethanol yields a crude ketone that is fractionated on a 15‑theoretical‑plate Oldershaw column at 5 mmHg. The heart-cut distills at 78‑80°C/5 mmHg with a purity surpassing 99.5% (GC‑FID). Residual ethanol is kept below 0.1% to comply with EU Regulation 1334/2008 on flavouring substances, and an S‑Fate routine according to JECFA evaluates genotoxic potential of the epoxide metabolite. In flavour houses, 2‑acetylthiazole is diluted to 1% in triacetin and incorporated at 1‑5 ppm in meaty, coffee, and roasted nut profiles. The aldehyde precursor drums bear a hazard label corresponding to UN 1987 (Alcohols, n.o.s.) when shipped as a solution to ensure compliance with the IMDG Code.Thiazole-cored fluorescent probes exploiting an intramolecular charge‑transfer (ICT) mechanism rely on the aldehyde function of 5-thiazolecarboxaldehyde as the anchoring point for extended conjugation. A representative system is the Knoevenagel condensation with 2‑(benzo[d]thiazol‑2‑yl)acetonitrile in the presence of piperidine in DMF at 80°C for 6 h. The resulting push‑pull chromophore exhibits a Stokes shift of 110 nm and a quantum yield of 0.34 in acetonitrile, values determined relative to fluorescein in 0.1N NaOH per ISO 20783‑1:2011. The pendant aldehyde allows subsequent Schiff‑base formation with o‑aminophenol to create a selective turn-on probe for Zn²⁺ in aqueous acetonitrile (detection limit 8 nM, measured by fluorescence titration with ZnClO₄ standards). Process-scale synthesis uses a 20‑L cylindrical glass reactor with overhead stirring and a reflux condenser; polymer‑bound piperazine or piperidine on silica facilitates catalyst recovery. After removal of the solid‑supported catalyst by vacuum filtration through a 10 µm PTFE membrane, the crude dye is purified by flash chromatography on silica gel 60 (230–400 mesh) with ethyl acetate/hexane (1:4 v/v). The isolated solid is dried in a vacuum oven at 30°C to a loss on drying of <0.2%. The material must be stored in amber glass vials under argon at −20°C to prevent aldol condensation products that appear as an HPLC doublet within 72 h at ambient light exposure. Research‑grade shipments are accompanied by a certificate documenting <0.1 ppm heavy metals by ICP‑MS and residual DMF below 500 ppm conforming to ICH Q3C limits for Class 2 solvents in non‑clinical studies.

Directed ortho-Metallation in the Synthesis of 2-Arylthiazole Ligands for C–H Activation Catalysis

Selective deprotonation at the thiazole C2 position by lithium diisopropylamide (LDA) in THF at −78°C permits direct electrophilic trapping with aryl disulfides or trimethyltin chloride to generate 2‑arylthio‑ or 2‑stannylthiazole intermediates. When 5-thiazolecarboxaldehyde is employed, the aldehyde group remains intact only if the lithiation is carried out with strict inverse addition of the substrate to a preformed LDA solution at −78°C; any rise above −65°C triggers rapid self‑condensation. The resulting stannane undergoes Stille coupling with aryl iodides under 5 mol% Pd(PPh₃)₄ in DMF at 90°C to deliver 2‑aryl‑5‑thiazolecarboxaldehydes with yields of 75–85% after column chromatography. These aldehydes serve as bidentate ligands for palladium‑catalysed oxidative Heck reactions. Ligand stock solutions are prepared at 0.05 M in degassed toluene and stored over molecular sieves 4Å; the free aldehyde content is checked weekly by FT‑IR carbonyl stretch at 1691 cm⁻¹ to confirm absence of hydrate formation. A representative ligand, 2‑(2,6‑dimethylphenyl)‑5‑thiazolecarboxaldehyde, is shipped in 1‑g or 5‑g Sure/Seal bottles to pre‑commercial catalyst screening laboratories. The material safety data sheet highlights that prolonged skin contact may cause sensitisation due to the thiazole‑aldehyde function and recommends rubber gloves tested under EN 374.

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Certification & Compliance

5-Thiazolecarboxaldehyde 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

5-Thiazolecarboxaldehyde (CAS 1003-02-1), systematic name thiazole-5-carbaldehyde, is supplied as a pale yellow crystalline solid with a molecular formula C₄H₃NOS and a relative molecular mass of 113.14 g·mol⁻¹. Two industrial grades predominate: a technical grade with purity ≥ 98.0% (HPLC, USP <621>) and a pharmaceutical intermediate grade certified to ≥ 99.5% with total specified impurities, including the 4-isomer and 5-thiazolecarboxylic acid, held below 0.10% each. Residual solvent content is controlled to ≤ 5000 ppm acetone and ≤ 3000 ppm methanol per USP <467> Option 2; the water content, determined by coulometric Karl Fischer titration (USP <921> Method Ic), is routinely ≤ 0.20% w/w. Bulk density of the milled powder ranges from 0.45 to 0.65 g·cm⁻³, and the material is packaged in amber HDPE drums purged to a headspace oxygen concentration of <0.1% v/v. A certificate of analysis referencing these limits accompanies every lot; the product is classified under REACH (EC No. 213-663-4) and is not subject to the Rotterdam Convention restrictions.

When Coupling with Primary Amines: Processing Window and Reactor Configuration

Maintaining a tightly controlled exotherm during Schiff base formation is the critical processing constraint when 5-thiazolecarboxaldehyde is condensed with aliphatic primary amines on a production scale. The reaction follows second-order kinetics with an activation energy reported in the literature at approximately 45–55 kJ·mol⁻¹; a temperature excursion of more than ±2 °C from the set point dramatically accelerates a competing bis-imine formation pathway, dropping the in-process HPLC purity of the mono-imine below 90 area% within 30 minutes. For a 50 kg batch, the standard configuration employs a 100 L glass-lined stirred reactor (Pfaudler WL series) equipped with a half-pipe jacket and a Huber Unistat 510w process thermostat delivering a temperature ramp rate of 0.5 °C·min⁻¹. Amine dosing is performed through a peristaltic pump (Watson-Marlow 530 series) at a fixed flow rate of 0.8–1.2 L·h⁻¹, corresponding to an amine addition stoichiometry of 0.50 mol equivalent over 40–60 min. The internal temperature, monitored via a Pt100 probe in a thermowell, must be held between −5 °C and 0 °C throughout the addition; a deviation exceeding +2 °C triggers an automatic interlock that stops the dosing pump until the jacket outlet fluid reaches −15 °C. Under these conditions, 95–97% conversion to the (E)-imine is achieved within 2 hours post-addition, as quantified by GC (Agilent 7890, DB-5 column, 30 m × 0.25 mm, FID at 280 °C). When the same condensation was performed on a 200 L scale in a non-jacketed stainless steel reactor relying solely on external cooling coils, an overshoot to 7 °C was observed in three out of five qualification batches, resulting in a 12–18% increase in the bis-imine impurity fraction and requiring a subsequent toluene recrystallization step that eroded yield by 8%. Pre-drying of 5-thiazolecarboxaldehyde in a vacuum oven (40 °C, 10 mbar, 4 h) to a moisture content of ≤ 0.05% is mandatory when the chosen amine has a pK_a below 5.5, as adventitious water catalyzes imine hydrolysis and slows the forward rate constant by a factor of approximately 3, according to kinetic traces measured via inline ReactIR 15 at 1650 cm⁻¹. In the synthesis of anticoagulant intermediates featuring a thiazole moiety, 5-thiazolecarboxaldehyde is employed in Knoevenagel condensations with active methylene compounds such as malononitrile. The aldehyde’s electrophilicity, quantified by a Hammett σ_m value of approximately 0.48 for the 5-thiazolyl group, enables base-catalyzed conditions (piperidine acetate, ethanol, 25 °C) to furnish the benzylidene adduct in yields exceeding 85% after 6 h.

Comparative Physicochemical Properties of 5- and 2-Thiazolecarboxaldehyde

Property	5-Thiazolecarboxaldehyde	2-Thiazolecarboxaldehyde	Units	Method
Melting point	42–44	−33 (liquid)	°C	DSC, 5 °C·min⁻¹
Boiling point	124–126 (20 mmHg)	72–74 (10 mmHg)	°C (kPa)	Siwoloboff method
Density (20 °C)	1.32	1.28	g·cm⁻³	Pycnometry
n_D²⁰	1.578	1.564	—	Abbe refractometer
Solubility in water (25 °C)	12	18	g·L⁻¹	Shake-flask, HPLC
log P (octanol/water)	0.64	0.51	—	HPLC, OECD 117
pK_a (conjugate acid)	0.92	0.45	—	Potentiometric, 25 °C, 0.1 M KCl
LUMO energy (B3LYP/6-31G(d))	−2.18	−1.93	eV	DFT calculation

The lower LUMO energy of the 5-isomer reflects the electron-withdrawing effect of the nitrogen atom para to the formyl substituent, making 5-thiazolecarboxaldehyde a more reactive electrophile in nucleophilic additions and cyclocondensations. This difference directly impacts process development: the 5-isomer reacts with thiosemicarbazide at 25 °C in 30 minutes to yield the thiosemicarbazone quantitatively, whereas the 2-isomer requires 6 hours at 60 °C to reach equivalent conversion as measured by in-situ ¹H‑NMR (Bruker 400 MHz, DMSO‑_d6). Steric factors further differentiate the positional isomers: the formyl group at C‑5 experiences minimal steric hindrance, while the 2‑position is flanked by both the ring sulfur and nitrogen atoms, reducing the accessibility of the carbonyl carbon to nucleophiles with a Tolman cone angle larger than 120°. Oxidative stability of 5-thiazolecarboxaldehyde is limited at ambient humidity. Exposure of a 5 g sample to air at 50% relative humidity and 22 °C leads to a 1.2% increase in 5-thiazolecarboxylic acid within 24 hours, as determined by HPLC (C18 column, 254 nm). Therefore, containers must be resealed under argon immediately after sampling, and bulk storage in nitrogen-flushed, 2–8 °C cold rooms is standard. Shelf life assigned from the date of manufacture is 12 months when the product is held under these conditions; a bi‑annual re‑test using USP <621> HPLC methodology is recommended for lots stored beyond 18 months. Contact with strong bases (pH > 10) induces aldol self-condensation, while exposure to sodium borohydride in methanolic solution generates an exotherm that can exceed 40 °C unless dosed portionwise.

What Differentiates 5-Thiazolecarboxaldehyde from 4-Thiazolecarboxaldehyde in Cross-Coupling Catalysis?

The scarcity of the 4-isomer (CAS 3364-80-5) in commercial supply chains has limited its benchmarking, but available data from patent literature and small‑scale heterocyclic synthesis indicate a marked difference in regioselectivity during palladium‑catalyzed direct C–H arylation. When 5‑thiazolecarboxaldehyde is subjected to reaction with aryl bromides in the presence of Pd(OAc)₂ (5 mol%), PCy₃·HBF₄ (10 mol%), and K₂CO₃ in N,N‑dimethylacetamide at 100 °C, arylation occurs exclusively at the 2‑position of the thiazole ring, as confirmed by single‑crystal X‑ray diffraction (Mo Kα, 0.71073 Å) of the isolated product. The formyl group at C‑5 acts as a directing group, chelating the palladium center through the carbonyl oxygen and enabling a five‑membered metallacycle intermediate with a calculated activation free energy (ΔG^‡) 12.5 kcal·mol⁻¹ lower than the seven‑membered ring that would be required for 4‑position metallation. In contrast, 4‑thiazolecarboxaldehyde, where the formyl group is adjacent to the nitrogen, delivers a mixture of 2‑ and 5‑arylated isomers in roughly 45:55 ratio under identical conditions, necessitating preparative HPLC separation. The divergent behavior is attributed to the electron density distribution in the frontier molecular orbitals: natural bond orbital (NBO) analysis at the B3LYP/6‑311+G(d,p) level reveals a natural charge at C‑2 of −0.31 e for the 5‑isomer versus −0.18 e for the 4‑isomer, rendering the 2‑position significantly more nucleophilic and selective toward oxidative addition when the formyl group occupies the 5‑position. The application of 5-thiazolecarboxaldehyde as a precursor for chiral oxazoline ligands in asymmetric hydrogenation has been validated on a pilot scale using a continuous-flow hydrogenator (ThalesNano H‑Cube Pro, 30 bar, 60 °C, 0.5 mL·min⁻¹ liquid flow, 10% Pd/C catalyst cartridge). Condensation with (S)‑tert‑leucinol followed by in‑situ cyclization in acetonitrile at reflux (82 °C) yields the 2‑(5‑thiazolyl)‑4‑tert‑butyloxazoline ligand with an enantiomeric excess of >98% (Chiralpak IA column, hexane/2‑propanol 90:10, 1.0 mL·min⁻¹, 254 nm). The equivalent sequence with 2‑thiazolecarboxaldehyde under identical conditions yields the oxazoline ligand in only 74% ee, a consequence of the increased steric bulk adjacent to the imine-forming carbon. Minimum ignition energy of the fine dust (125 µm D₅₀) of 5‑thiazolecarboxaldehyde is measured at 35 mJ (EN 13821); accordingly, all powder handling operations must be conducted under nitrogen inerting with an oxygen concentration maintained below 8% v/v and grounding resistance less than 10⁶ Ω.

Parameter	Acceptable Limit	Reference Standard
Purity (HPLC, area%)	≥ 99.5% (Pharma grade)	USP <621>
Water content	≤ 0.20% w/w	USP <921> Ic
Sulfated ash	≤ 0.10%	USP <281>
Arsenic (As)	≤ 0.15 µg·g⁻¹	ICH Q3D, Class 1
Lead (Pb)	≤ 0.50 µg·g⁻¹	ICH Q3D, Class 1
Cadmium (Cd)	≤ 0.20 µg·g⁻¹	ICH Q3D, Class 1
Mercury (Hg)	≤ 0.15 µg·g⁻¹	ICH Q3D, Class 1
Cobalt (Co)	≤ 0.50 µg·g⁻¹	ICH Q3D, Class 2A
Nickel (Ni)	≤ 2.50 µg·g⁻¹	ICH Q3D, Class 2A
Vanadium (V)	≤ 2.50 µg·g⁻¹	ICH Q3D, Class 2A
Residual acetone	≤ 5000 ppm	USP <467>
Residual methanol	≤ 3000 ppm	USP <467>