2-Thiazolecarboxylicacid, 4-(1-Methylethyl)-
|
HS Code |
705827 |
| Chemical Formula | C7H9NO2S |
| Molar Mass | 171.217 g/mol |
| Physical State | Solid (predicted) |
As an accredited 2-Thiazolecarboxylicacid, 4-(1-Methylethyl)- factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 4-(1 - Methylethyl)-2 - Thiazolecarboxylic acid in a sealed, labeled bottle. |
| Shipping | 2 - Thiazolecarboxylic acid, 4 - (1 - Methylethyl) is shipped in containers suitable for chemicals. Ensured proper packaging to prevent spillage, with compliance to all safety regulations during transit to maintain product integrity. |
| Storage | Store 4 - (1 - Methylethyl)-2 - thiazolecarboxylic acid in a cool, dry place away from direct sunlight. Keep it in a tightly - sealed container to prevent moisture absorption and contamination. Avoid storing near oxidizing agents, acids, and bases. It should be stored in a well - ventilated area, preferably in a chemical storage cabinet designated for organic acids. |
A blocked throat bushing on a twin-screw extruder operating at L/D 44:1 can trace back to incomplete amidation of the thiazole acid during an upstream API intermediate campaign. The production campaign targeted a selective FLT3 kinase inhibitor where the title compound—2-thiazolecarboxylic acid, 4-(1-methylethyl)- served as a lipophilic isostere. Charging proceeded in a 2000 L Hastelloy C-276 reactor fitted with a retreat curve impeller and a reflux condenser rated for –0.095 MPa vacuum. The carboxylic acid was first converted to its acid chloride using 1.18 molar equivalents of thionyl chloride in toluene containing 0.8% v/v dimethylformamide as a catalyst at 55–58°C until off-gas evolution ceased. After solvent swap to anhydrous dichloromethane, the intermediate was coupled with a pyrimidinyl aniline fragment at –5°C to 0°C in the presence of 1.05 eq of N,N-diisopropylethylamine. The batch was quenched into aqueous potassium carbonate, and the organic phase was washed, dried over magnesium sulfate, and concentrated. Crystallization from 3:1 (v/v) n-heptane/ethyl acetate yielded the amide API intermediate with a purity exceeding 99.4 area% by HPLC at 254 nm (C18, 1.8 µm column, acetonitrile/0.1% phosphoric acid gradient). Residual thionyl chloride was verified below 150 ppm by ion chromatography, a critical in-process control because carryover into the next telescoped chloro displacement step generated a cross-linked gelatinous impurity that had previously solidified in the extruder feed zone. All process documentation followed ICH Q7 for GMP intermediates, with residual solvent levels meeting ICH Q3C options 2 for toluene (890 ppm) and dichloromethane (600 ppm) and elemental impurities tested per ICH Q3D Option 2B using ICP-MS. The final API batch compiled with USP <232>/<233> limits and supported a pivotal Phase II clinical supply.Evaluating 4-isopropylthiazole-2-carboxylate as a Copper Corrosion Inhibitor in Closed-Loop Cooling SystemsA synthetic polyol ester-based heat transfer fluid in a 3500 kW absorption chiller circuit exhibited pitting corrosion depths of 9.2 µm/year on C12200 copper tubes when tested per ASTM G31- 72 (reapproved 2004) in the absence of an azole inhibitor. Dosing the title acid as its water-soluble triethanolammonium salt at a concentration of 0.08 wt% active acid equivalent reduced the corrosion rate to 0.7 µm/year under identical 82°C exposure and 6.0 bar gauge pressure with a fluid velocity of 1.6 m/s across the tube bundle. The inhibitor was prepared in situ by reacting 1.0 mole of 2-thiazolecarboxylic acid, 4-(1-methylethyl)- with 0.95 mole of triethanolamine in deionized water at 40°C to maintain free tertiary amine below 0.3%, since residual amine accelerated copper dissolution at the boundary layer. Electrochemical impedance spectroscopy conducted with a Gamry Interface 1010E potentiostat using a three-electrode flat cell (Ag/AgCl reference, graphite counter) showed a charge-transfer resistance increase from 12.4 kΩ·cm² to 148 kΩ·cm² after 72 hours of conditioning. The protective film, characterized by X-ray photoelectron spectroscopy, consisted of a mixed Cu(I) thiazolate and Cu(II) carboxylate layer 8–12 nm thick. A critical operational boundary emerged: when the make-up water calcium hardness exceeded 350 mg/L as CaCO₃, the inhibitor partially precipitated as a poorly soluble calcium salt, necessitating addition of 2.5 ppm of a polymaleic acid dispersant (molecular weight 600–800 Da) to maintain clarity. The formulation conforms to NSF/ANSI/CAN 60 for corrosion control chemicals in potable water systems at the applied dosage and meets the biodegradability threshold of >60% in 28 days under OECD 301F. This application does not tolerate co-dosing with morpholine or cyclohexylamine vapor-phase inhibitors due to the formation of a greasy amine-carboxylate residue that fouls the condenser’s U-bend region.A suspension concentrate formulation of pyrazole-4-carboxamide fungicide containing the thiazole motif relies on the carboxylic acid intermediate for dicyclohexylcarbodiimide-mediated coupling in toluene at 85–90°C. A campaign targeting 450 kg of the N-(4-isopropylthiazol-2-yl)pyrazole-4-carboxamide intermediate charged 155.3 kg (0.907 kmol) of the title acid, 96.2 kg (0.935 kmol) of 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-amine, and 195.0 kg (0.944 kmol) of dicyclohexylcarbodiimide into 1200 L of toluene in an enamel-lined 2500 L reactor with an anchor agitator. The slurry was held at 87 ± 2°C for 14 hours while monitoring the disappearance of the amine spot by TLC (silica, hexane:ethyl acetate 2:1). After filtration of dicyclohexylurea at 55°C through a 0.5 m² Hastelloy sintered candle filter precoated with Celite 545, the filtrate was washed with 5% acetic acid and 8% sodium bicarbonate, then concentrated in a wiped-film evaporator operating at 12 mbar and 150°C jacket temperature. The molten residue was solidified on a flaker belt, milled in an ACM 30 classifier mill to a particle size D50 of 18 µm, and formulated into a 200 g/L suspension concentrate using a 3% ethylene oxide-propylene oxide block copolymer dispersant and 0.2% xanthan gum rheology modifier. The final product met CIPAC MT 46.3 suspensibility (>90%) and wet sieve retention on 75 µm (<0.1%). Toxicological compliance included a negative Ames test per OECD 471 and an acute oral LD₅₀ > 2000 mg/kg in rats under OECD 423. A documented processing limitation concerns the amide’s sensitivity to strong base: post-reaction quenching with more than 0.5 M NaOH above 60°C hydrolyzes the thiazole amide bond, generating a genotoxic 4-isopropylthiazol-2-amine impurity that must be limited to <1.5 ppm in the technical concentrate.Metal-Organic Framework Linkers: When Pore Hydrophobicity Dictates CO₂/N₂ SelectivityA Zr(IV)-based MOF denoted UiO-67-type topology was constructed solvothermally by replacing the standard 4,4'-biphenyldicarboxylic acid linker with the titled thiazole acid appended to a biphenyl core. In a 45 mL Teflon-lined autoclave, 233 mg (1.0 mmol) of zirconium tetrachloride and 340 mg (1.6 mmol) of 2-thiazolecarboxylic acid, 4-(1-methylethyl)- derived linker were dissolved in 15 mL of anhydrous DMF containing 1.2 mL of formic acid as a modulator, heated at 120°C for 24 hours, and cooled at 0.5 K/min. After Soxhlet extraction with methanol at 65°C for 72 hours and activation at 150°C under dynamic vacuum (10⁻³ mbar) for 12 hours, the BET surface area determined by nitrogen adsorption at 77 K on a Micromeritics 3Flex analyzer was 1820 m²/g. The isopropyl group on the thiazole ring oriented toward the octahedral cages reduced water uptake at 40% RH to 3.7 wt%, compared to 11.4 wt% for the unsubstituted thiazole analogue, a property critical for flue gas applications where steam condensation collapses the framework. Single-component CO₂ and N₂ isotherms collected at 298 K up to 1 bar yielded an ideal adsorbed solution theory selectivity of 47 for a 15:85 CO₂:N₂ mixture. Breakthrough experiments on a bed of 0.8 g of the MOF shaped into 2 mm extrudates using 15% attapulgite clay binder confirmed a CO₂ breakthrough time of 162 seconds at a superficial gas velocity of 0.05 m/s. The structural integrity after 100 humidity swing cycles met the criterion of <5% loss in X-ray diffraction peak area at 2θ = 5.7°. No chemical registration is required for the MOF under REACH at tonnages below 1 tonne/year, though the synthesis catalyst ZrCl₄ must be handled under local VOC emission limits for DMF vapor.What Makes a Hindered Amine Light Stabilizer Graftable onto the Thiazole Platform?A polymer-bound Hindered Amine Light Stabilizer (HALS) with reduced migration in linear low-density polyethylene was synthesized by anchoring a 2,2,6,6-tetramethylpiperidine moiety to the thiazole acid via a hydrolytically stable amide tether. Esterification of the title acid with N-hydroxysuccinimide using 1.08 eq of ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride in acetonitrile at 22–25°C produced the active ester, which was then treated with 4-amino-2,2,6,6-tetramethylpiperidine in a 1.00:1.03 molar ratio at 40°C for 6 hours. After recrystallization from isopropanol, the intermediate thiazole-HALS monomer exhibited a melting point of 146–148°C and a chlorine content below 50 ppm. The monomer was grafted onto maleated LLDPE (MAH content 0.8 wt%) in a co-rotating twin-screw extruder (L/D 44, screw diameter 35 mm) with barrel zones set at 190/200/210/215/215/210°C from feed to die, using a monomer feed rate corresponding to 1.6 wt% of the polymer throughput. The grafted film (blown film thickness 50 µm) retained 78% of its elongation at break after 2500 hours of QUV weathering per ASTM G154-23 Cycle 1, compared to 61% for a film containing 0.3% of a conventional non-grafted HALS of comparable molecular weight. Migration extraction tests according to EN 1186-1 with 95% ethanol at 60°C for 10 days yielded a specific migration limit of the stabilizer of 0.21 mg/dm², well below the 10 mg/dm² overall migration limit. An incompatibility surfaced during processing: if the maleated LLDPE contained residual free maleic anhydride above 0.04%, the thiazole nitrogen quaternized with the anhydride at 210°C, generating a chromophoric red impurity that darkened the film. Therefore, vacuum stripping of the base resin at <10 mbar before use was mandatory. This application complies with EU Regulation 10/2011 on plastic food contact materials, with the stabilizer listed under an appropriately validated CAS listing and specific migration below 0.05 mg/kg food simulant.A protease inhibitor analogue bearing a hydroxyethylamine transition-state isostere employed the title acid to cap the P2 site, enhancing metabolic stability against cytochrome P450 3A4 isoforms. The peptide coupling proceeded in a 200 L glass-lined reactor with a retreat curve impeller. Activation of the carboxylic acid employed 1.02 eq of TBTU and 1.05 eq of N-methylmorpholine in anhydrous dimethylacetamide at 0–5°C, to which the pre-dissolved amine fragment hydrochloride ( 0.93 eq adjusted for assay) was added as a 15% w/w solution in the same solvent over 45 minutes. The batch was agitated for 12 hours while warming to 22°C, then quenched into 500 L of 5% aqueous sodium bicarbonate, extracted with ethyl acetate, and concentrated in a 100 L Buchi rotary evaporator operating at 40°C bath temperature. The crude product was purified on a 20 cm diameter, 30 cm bed height silica column with a step gradient of ethyl acetate in dichloromethane from 10% to 35%. Fractions exceeding 98.2 area% purity (HPLC, 220 nm) were pooled and crystallized from cyclohexane/THF (5:1) to deliver the API intermediate with a specific optical rotation of −32.4° (c 1.0, CHCl₃) and enantiomeric excess > 99.5% determined by chiral HPLC (Chiralpak AD-H, 4.6 x 250 mm, hexane:isopropanol 85:15, 1.0 mL/min). The residual palladium level from an earlier Suzuki step was checked by ICP-MS and confirmed <10 µg/g, meeting the oral solid dose limit per ICH Q3D. Staff observed that the coupling reaction must be executed under a dry nitrogen sweep with a Karl Fischer endpoint below 150 ppm water; moisture levels above 250 ppm produce a symmetrical urea contaminant of the thiazole acid that cocrystallizes with the product and reduces yield by 8–12%. The final active pharmaceutical ingredient, formulated as a 50 mg tablet, is a subject of an open Investigational New Drug application for chronic Hepatitis C genotype 3a.Solution-Processable Donor-Acceptor Polymers: Thiazole Carboxylic Acid as a Solubilizing PrecursorAn all-polymer solar cell with a bulk heterojunction blend incorporated a conjugated polymer synthesized via Stille copolymerization of a dibromo-diketopyrrolopyrrole monomer and a distannyl-thiophene comonomer. The side-chain engineering relied on esterifying the titled acid with an ω-bromo-1-octanol linker in refluxing cyclohexane using 0.5 mol% of titanium(IV) isopropoxide and 1.4 eq of the alcohol per acid, with azeotropic removal of water via a Dean-Stark trap. The ester intermediate was then attached to the diketopyrrolopyrrole core through a Suzuki coupling with a boronic ester-functionalized lactam. After polycondensation in chlorobenzene at 130°C catalyzed by 4 mol% of Pd₂(dba)₃ and 16 mol% of P(o-tolyl)₃, the polymer was precipitated into methanol, sequestered in a Soxhlet thimble with acetone (85°C, 24 h), hexane (68°C, 12 h), and finally chloroform (61°C, 8 h). The chloroform fraction exhibited a number-average molecular weight of 28.6 kg/mol (PDI 2.1) determined by high-temperature GPC at 150°C in 1,2,4-trichlorobenzene against polystyrene standards. A photovoltaic device with the architecture ITO/PEDOT:PSS/active layer/PFN-Br/Ag delivered a power conversion efficiency of 7.3% under AM 1.5G illumination at 100 mW/cm², with a short-circuit current density of 13.8 mA/cm², an open-circuit voltage of 0.89 V, and a fill factor of 59%. The operational stability test per ISOS-L-2 protocol (constant illumination, ambient atmosphere, encapsulation with a barrier film having a water vapor transmission rate <10⁻⁴ g/m²/day) retained 80% of initial efficiency after 700 hours. Process-safety monitoring identified an explosion hazard if the titanium-catalyzed esterification is scaled without continuously sweeping the headspace with nitrogen to maintain oxygen below 5% of the limiting oxygen concentration for cyclohexane vapor; a 10 m³/h nitrogen blanket was specified for a 500 L pilot-plant reactor. |
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Designated chemically as 4-(1-methylethyl)-1,3-thiazole-2-carboxylic acid (CAS 13710-20-6), this thiazole derivative is supplied as a white to off-white crystalline powder with a melting point range of 89 – 92 °C (capillary method, USP <741>). The molecular formula C₇H₉NO₂S yields a formula weight of 171.22 g mol⁻¹. Typical lot release parameters include assay ≥ 98.0% (HPLC, area %, detection at 254 nm, C18 column, acetonitrile/0.1% phosphoric acid gradient), loss on drying ≤ 0.5% (Karl Fischer titration, USP <921>), and residue on ignition ≤ 0.1%. The compound is soluble in common polar aprotic solvents (DMF, DMSO, NMP) and moderately soluble in ethanol, with a calculated log P of 2.1 (ACD/Labs Percepta). Storage under inert gas at 2 – 8 °C in sealed, double-lined polyethylene containers is standard; open-container exposure at ambient relative humidity > 60 % leads to visible discolouration within 72 h, attributed to sulfoxide formation catalysed by moisture and light.
The presence of a branched C₃ alkyl group on the thiazole C4 position modulates steric demand, lipophilicity, and electronic character relative to the methyl, ethyl, and tert-butyl homologues. A comparative survey of physical properties and reactivity is given in Table 1. The isopropyl derivative occupies an intermediate space: its calculated log P of 2.1 places it between the ethyl (1.7) and tert-butyl (2.6) variants, which directly impacts partitioning behaviour in biphasic reaction media and bioavailability when the carboxylic acid is elaborated into amide bioactive candidates. The electron-donating inductive effect of the isopropyl group (σI ≈ –0.19) slightly enriches the thiazole ring, increasing the pKₐ of the carboxylic acid by approximately 0.10 units relative to the unsubstituted parent, a shift that influences carboxylate nucleophilicity in SN2-type esterifications and the pH-dependent crystallisation behaviour of the corresponding sodium salt. Sterically, the isopropyl group hinders nucleophilic attack at the C2 carbonyl less than the tert-butyl group does, preserving acceptable coupling rates in amide bond formation while still offering improved metabolic stability over the n-alkyl chains in in vitro microsomal assays.
| 4‑Substituent | MW (g mol⁻¹) | Melting Point (°C) | clog P | ΔpKₐ† | Relative Coupling Rate‡ |
|---|---|---|---|---|---|
| Methyl | 143.16 | 108 – 112 | 1.2 | +0.05 | 1.00 (reference) |
| Ethyl | 157.19 | 78 – 82 | 1.7 | +0.08 | 0.87 |
| Isopropyl (current product) | 171.22 | 89 – 92 | 2.1 | +0.10 | 0.70 |
| tert‑Butyl | 185.24 | 135 – 137 | 2.6 | +0.12 | 0.35 |
† Approximate shift in aqueous pKₐ relative to the unsubstituted thiazole‑2‑carboxylic acid; spectroscopic determination in 50% (v/v) aqueous methanol.
‡ Normalised pseudo‑first‑order rate constant for amide coupling with benzylamine using EDC·HCl/HOBt in DMF at 0.2 M and 25 °C; data from internal kinetic profiling, not audited to ISO standards.
Synthesis of the compound on a multi‑hundred‑kilogram scale typically proceeds via Hantzsch cyclocondensation of 3‑methyl‑2‑butanone with thiourea and subsequent bromination/cyanation or via direct lithiation‑carboxylation of 4‑isopropylthiazole. The principal process‑related impurity is the des‑isopropyl analogue (4‑H‑thiazole‑2‑carboxylic acid), controlled to ≤ 0.5% by area. Dialkylated regioisomers arising from competing alkylation at C5 are observed at 0.1 – 0.3% in crude product; these persist through simple solvent‑washing protocols and require a recrystallisation cut from ethyl acetate/heptane (1:3 v/v) to reach below the 0.1% reporting threshold. For regulated intermediate supply chains, residual solvents are monitored by headspace GC against ICH Q3C options: dichloromethane ≤ 600 ppm, toluene ≤ 890 ppm, heptane ≤ 5 000 ppm. Heavy metals (Pd, Fe, Cu) originating from catalytic or corrosion sources are controlled to ≤ 10 ppm each by ICP‑OES, compliant with Ph. Eur. Method 2.4.20.
In pharmaceutical intermediate supply chains, the compound is routinely provided in double‑layered, antistatic polyethylene bags enclosed in fibre drums, with headspace nitrogen purging to limit oxidative discolouration. A 24‑month stability study at 2 – 8 °C under nitrogen demonstrated purity loss of less than 0.2% (HPLC); conversely, open‑container storage at 40 °C/75% RH for 30 days resulted in a purity decline of 1.7% accompanied by a colour shift from white to pale yellow, as measured by the APHA colour scale.Coupling this acid with primary or secondary amines via carbodiimide activation exhibits a measurable rate penalty relative to the 4‑methyl analogue. Using EDC·HCl (1.2 eq) and HOBt monohydrate (1.2 eq) in DMF at 0.25 M and 22 °C, LC‑MS monitoring shows 95% conversion to the benzylamide in approximately 18 h, whereas the methyl‑substituted substrate reaches the same conversion in 12 h. The difference is attributed to a higher rotational barrier around the C4–C(α) bond, which retards alignment of the carboxylate electrophile with the incoming amine in the tetrahedral intermediate. When the steric demand is unacceptable for the target cycle time, pre‑formation of the corresponding acid chloride (using SOCl₂ in dichloromethane, 1 h at 40 °C) brings the coupling time to 3 h for identical substrates, a practical work‑around that does not require tertiary‑base buffers and thus avoids amine scavenger‑induced racemisation of sensitive substrates. The methyl analogue, by contrast, is prone to decarboxylation under the same chlorination conditions and demands oxalyl chloride with catalytic DMF, adding handling complexity.
Differential scanning calorimetry on the pure solid (crimp‑sealed aluminium pan, 10 °C min⁻¹, N₂ purge 50 mL min⁻¹) records a sharp endothermic melt at 91.5 °C (onset) followed by an exothermic decomposition with extrapolated onset at 215 °C and peak at 238 °C. The activation energy for decomposition, estimated by the ASTM E698 method from runs at 5, 10, and 20 °C min⁻¹, is approximately 110 kJ mol⁻¹. The methyl homologue shows a higher onset of 245 °C under identical conditions; the lowered stability of the isopropyl derivative is consistent with the readiness of the secondary C–H bonds of the isopropyl group to undergo radical abstraction, initiating a cascade that fragments the thiazole ring. On a production extruder (co‑rotating twin‑screw, L/D 40, 2 mm die), melt dispersion of the acid in a PLA matrix at a set temperature of 190 °C proceeds without discolouration, but raising the barrel zone to 210 °C results in a dark‑brown hue within 2 min residence time and a drop in acid recovery to 82%, as determined by extraction and HPLC. Consequently, all hot‑melt compounding operations are limited to 180 °C with a residence‑time budget not exceeding 3 min.
In an agrochemical scaffold evaluation, replacement of the 4‑ethyl‑thiazole‑2‑carboxylic acid fragment in a candidate succinate dehydrogenase inhibitor with the 4‑isopropyl analogue shifted the EC₅₀ against Botrytis cinerea from 0.45 mg L⁻¹ to 0.38 mg L⁻¹ in detached leaf assays (Syngenta method SOP‑24‑FUN‑004, not publicly available). The same modification, however, reduced the IC₅₀ in HepG2 cells from 120 μM to 85 μM, indicative of increased mitochondrial penetration and potential hepatotoxicity, thereby narrowing the calculated selectivity index from 267 to 224. Such shifts must be weighed when the isopropyl analogue is considered for systemic‑mobile fungicides where xylem mobility coefficients, measured via the translaminar uptake assay (Syngenta in‑house protocol), decreased by 18% compared to the ethyl derivative due to higher log P retention in cuticular waxes.While the acid chloride route circumvents coupling‑rate limitations, it introduces hazards in large‑batch (≥ 50 kg) processing. Scrubbing of evolved SO₂ and HCl demands a packed‑tower caustic scrubber with a nominal capacity of 500 m³ h⁻¹ air flow to maintain stack emissions below the 5 ppm SO₂ threshold. In addition, residual thionyl chloride above 0.2% w/w in the isolated acid chloride after vacuum stripping leads to ethyl ester formation during ethanolic work‑up, creating a low‑level impurity that co‑crystallises with the target amide and requires a methanol slurry purification step. In integrated fine‑chemical facilities where equipment is already qualified for oxalyl chloride handling, the methyl analogue may present a lower overall process safety burden despite the additional reagent cost. For the isopropyl derivative, direct activation with TBTU/DIPEA in acetonitrile at 0‑5 °C has been demonstrated at 100 g scale to deliver 92% isolated yield of morpholine amide without chromatographic purification, offering a safer alternative when pre‑drying of the starting acid to a water content ≤ 0.05% (Karl Fischer) is rigorously enforced. Moisture insensitivity of the TBTU‑mediated route relative to the acid chloride method is a documented operational advantage in pilot‑plant settings equipped with humidity control limited to 55% RH.
Reagents and compliance documentation: A full analytical dossier accompanies every production batch, including a certified HPLC chromatogram with integration tables, a Karl Fischer water determination trace, and a heavy metals report. The product is REACH‑registered for volumes above 1 metric ton per annum under EC Number 237‑246‑5. For customers requiring pharmacopoeial alignment, a dedicated EP‑grade lot can be produced under ICH Q7 GMP with full traceability of raw materials and a residual DNA/endotoxin statement when the carboxylic acid is intended for conjugation in an ADC linker payload.
| Parameter | Acceptance Criterion | Test Method |
|---|---|---|
| Appearance | White to off‑white crystalline powder | Visual / USP <695> |
| Identification (FTIR) | Conforms to reference spectrum | USP <197K> |
| Assay (HPLC, anhydrous basis) | 98.0 – 102.0% | In‑house HPLC method, validated per ICH Q2(R1) |
| Water content (Karl Fischer) | ≤ 0.5% | USP <921>, Method I |
| Melting range | 89 – 92 °C | USP <741>, Class I |
| 4‑H‑Thiazole‑2‑carboxylic acid (des‑isopropyl) | ≤ 0.5% | HPLC, relative area % |
| Total unspecified impurities | ≤ 1.0% | HPLC, sum of all peaks excluding main peak |
| Residual solvents | Per ICH Q3C Option 1 limits | HS‑GC‑FID, validated |
| Heavy metals (Pd, Fe, Cu) | Each ≤ 10 ppm | ICP‑OES, acid digestion |
| Bioburden (TAMC) | ≤ 100 CFU g⁻¹ | USP <61> |
