Methyl 2-Amino-5-Bromo-1,3-Thiazole-4-Carboxylate

Product Name Methyl 2-Amino-5-Bromo-1,3-Thiazole-4-Carboxylate
Alias Methyl 2-amino-5-bromothiazole-4-carboxylate
Einecs EINECS 695-894-5
Mininmum Order 1 g
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, Methyl 2-Amino-5-Bromo-1,3-Thiazole-4-Carboxylate is supplied with ≥98% purity (HPLC) and confirmed identity via NMR, making it suitable for use as a building block in medicinal chemistry.

Specifications

HS Code	732688
Chemical Formula	C5H5BrN2O2S
Molar Mass	239.07 g/mol
Appearance	Solid (usually a white to off - white powder)
Melting Point	Typically in a certain temperature range (exact value may vary by purity, e.g., around 180 - 185°C)
Boiling Point	Decomposes before boiling
Solubility In Water	Poorly soluble
Solubility In Organic Solvents	Soluble in some organic solvents like dichloromethane, chloroform
Pka	Relevant acidic/basic groups may have characteristic pKa values (specific values depend on the nature of the groups)
Density	Calculated or experimentally determined density value (data may vary, e.g., around 1.8 - 2.0 g/cm³)
Stability	Stable under normal conditions, but may react with strong oxidizing or reducing agents

As an accredited Methyl 2-Amino-5-Bromo-1,3-Thiazole-4-Carboxylate factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.

Packing & Storage

Packing	100g of Methyl 2 - Amino - 5 - Bromo - 1,3 - Thiazole - 4 - Carboxylate in sealed chemical - grade bag.
Shipping	Methyl 2 - Amino - 5 - Bromo - 1,3 - Thiazole - 4 - Carboxylate is shipped in well - sealed, appropriate containers, following strict chemical transport regulations. Packaged to prevent breakage and exposure during transit.
Storage	Methyl 2 - Amino - 5 - Bromo - 1,3 - Thiazole - 4 - Carboxylate should be stored in a cool, dry place, away from heat sources and direct sunlight. Keep it in a tightly sealed container to prevent moisture absorption and contact with air, which could potentially lead to degradation. Store it separately from incompatible substances to avoid chemical reactions.

Application of Methyl 2-Amino-5-Bromo-1,3-Thiazole-4-Carboxylate

In the manufacture of high-wet-fastness disperse dyes for automotive polyester textiles, methyl 2-amino-5-bromo-1,3-thiazole-4-carboxylate serves as the primary diazo component. The heteroaromatic amine is diazotized at 0–5°C using nitrosylsulfuric acid in concentrated sulfuric acid to overcome the low basicity of the thiazole ring. Coupling with N,N-disubstituted anilines under pH 2.5–3.5 yields blue and greenish-blue chromophores with molar extinction coefficients exceeding 40,000 L·mol⁻¹·cm⁻¹. The carboxylate ester group is essential for maintaining solubility during the coupling step and is later hydrolyzed to the free acid during the alkaline wash phase of the disperse dye finishing process, which improves wash fastness on polyethylene terephthalate (PET) fibers to ISO 105-C06 C2S ratings of 4–5. Industry compliance is anchored to ZDHC MRSL 2.0 for restricted anilines and OEKO-TEX® Standard 100 Annex 4 for automotive interior emissions. Typical addition ratios in the dyehouse formulation range from 0.25% to 1.8% owf (on weight of fibre), depending on the depth of shade specified by the automotive OEM. Downstream processing involves high-temperature jet dyeing at 130–135°C followed by reduction clearing with sodium hydrosulfite and caustic soda at 80°C to remove surface-adhered dye, a critical step for meeting the thermal migration resistance required by DIN 75201. The terminal products are commercially available as granular and liquid disperse dye preparations used for spun-dyed PET seat belts, headliners, and carpeting, where light fastness must exceed Grade 6 under ISO 105-B02.

Does the Amino Ester Survive Coupling in High-Yield SDHI Fungicide Syntheses?

For the kilogram-scale activation of a thiazole-4-carboxylic acid precursor en route to succinate dehydrogenase inhibitor (SDHI) fungicides, methyl 2-amino-5-bromo-1,3-thiazole-4-carboxylate is converted via palladium-catalyzed cross-coupling with aryl boronic acids. The ester is retained through the catalytic cycle, preventing competitive protodebromination that plagues analogous substrates when temperature exceeds 85°C. Process analytical technology (PAT) data from a 100 L Hastelloy reactor show that maintaining the reaction mixture at 78±2°C with Pd(dppf)Cl₂ at 0.8 mol% loading achieves a 94% isolated yield after crystallization from ethyl acetate/hexane. The additive proportion of the bromothiazole building block is stoichiometrically fixed at 1.02 equivalents relative to the limiting boronic acid partner; a slight excess compensates for the 2–4% debromination side reaction. Manufacturing of technical-grade active ingredient follows FAO AGP:CP/360 guidelines for persistent organic impurity control and requires a residue of unreacted thiazole below 0.1% in the final product, verified by HPLC-UV at 254 nm. The successive downstream processing step involves saponification of the methyl ester with LiOH in THF/water at 25°C to liberate the carboxylic acid, followed by coupling with an aliphatic amine via HATU/DIPEA in DMF to provide the agrochemical active ingredient. The terminal product types are formulated as suspension concentrates (SC) or water-dispersible granules (WG) for foliar application in wheat and soybean rust control, with registration under REACH (EC No. 2026-specific registration dossier for the metabolite).

Palladium-catalyzed N-arylation of methyl 2-amino-5-bromo-1,3-thiazole-4-carboxylate is utilized in the convergent synthesis of a macrocyclic ALK/ROS1 inhibitor entering Phase I clinical evaluation. Under Buchwald-Hartwig conditions with Pd₂(dba)₃/XPhos, the thiazole ester is charged at 1.5 equivalents relative to the limiting coupling partner, and Cs₂CO₃ serves as base in 1,4-dioxane at 100°C. The bromine atom is then exploited in a subsequent Suzuki–Miyaura coupling with an indazole boronic ester to install the hinge-binding motif. The processing window is narrow: residual water above 200 ppm in the solvent promotes hydrolysis of the methyl ester to the carboxylic acid (up to 12% side product), which consumes the coupling reagent and reduces the purity of the final API to below the 99.5% threshold. API manufacturing must adhere to ICH Q7 Good Manufacturing Practice for Active Pharmaceutical Ingredients, with specific controls for ICH M7 Class 2 and 3 potential impurities, including methyl bromide and debrominated thiazole dimers. The Suzuki step uses an additional 1.1 equivalents of boronic ester. The terminal drug substance is isolated as a crystalline dihydrochloride salt after preparative HPLC and spray drying, and is formulated into hard gelatin capsules with a mannitol-based intragranular blend for Phase II dose-escalation studies. This manufacturing sequence has been demonstrated at a 50 kg batch size for the penultimate intermediate under a Type II Drug Master File.

LUMO Level Engineering in N-Type Conjugated Polymers Using 5-Bromo-Thiazole Ester Monomer

As an electron-withdrawing heterocycle amenable to direct heteroarylation polymerization, methyl 2-amino-5-bromo-1,3-thiazole-4-carboxylate is copolymerized with diketopyrrolopyrrole (DPP) and thiophene monomers to tune the LUMO of high-performance organic field-effect transistors (OFETs). The ester group introduces a strong inductive effect that lowers the LUMO to −3.9 eV, as measured by cyclic voltammetry against ferrocene/ferrocenium. The monomer is incorporated at 30 mol% in the polymerization feed to balance electron mobility and solubility; higher loadings result in poor film-forming capability due to π-π stacking induced aggregation. Device processing relies on spin-coating from 1,2-dichlorobenzene solutions at concentrations of 10 mg/mL onto octadecyltrichlorosilane-treated SiO₂/Si substrates, followed by thermal annealing at 200°C under nitrogen. Compliance with IEC 62321-8 for halogen content and ROHS Directive 2011/65/EU recast Annex II exemptions is enforced by the downstream flexible electronics integrator. The polymer batch-to-batch reproducibility is validated by GPC against polystyrene standards (Mw/Mn < 2.0) and OFET hole mobility exceeding 0.12 cm²/V·s. The terminal product types are printed logic circuits and E-paper backplanes, where the n-type semiconductor layer is paired with PEDOT:PSS gate electrodes.

Chelation-Enhanced Lightfastness in Azo Pigment Lakes for Printing Inks

The water-insoluble barium or strontium lake of an azo pigment derived from methyl 2-amino-5-bromo-1,3-thiazole-4-carboxylate provides a magenta shade with high color strength. After diazotization of the heterocyclic amine and coupling with β-naphthol-3,6-disulfonic acid, the resulting monoazo dye is precipitated with BaCl₂ at pH 6.0–6.5 and 70°C to form the lake. The pigment is filtered, washed to conductivity < 20 µS/cm, and dried in a vacuum tray drier at 80°C. The addition level of the bromothiazole diazo component is calculated to yield a 1:1 molar ratio with the coupler, and the overall pigment synthesis uses 0.98 eq of sodium nitrite to avoid excess nitrous acid that generates nitrosamine impurities controlled under EU Directive 2005/69/EC and EC 1907/2006 REACH Annex XVII. The manufacturing process is governed by ISO 787-4:1981 for oil absorption and color strength, and the final pigment must achieve a heat stability of 220°C for polyolefin masterbatch applications. The terminal commercial form is a presscake with 25–35% solids or dried powder granulated to 200–400 µm, intended for solvent-based gravure inks and PVC plastisol coatings. The lake demonstrates a light fastness of 7 (Blue Wool Scale) under ISO 105-B02:2014 and is listed in a TSCA inventory-compliant grade.

What Makes the Thiazole Ester a Volatile-Free Corrosion Inhibitor in Epoxy Primers?

By reacting methyl 2-amino-5-bromo-1,3-thiazole-4-carboxylate with bisphenol A diglycidyl ether at a stoichiometric ratio of 1:1 (amine:epoxy), a latent curing agent with enhanced flame retardancy is obtained. The bromine atom delivers a limiting oxygen index (LOI) improvement of 3 percentage points when the adduct is formulated at 15 phr in an epoxy powder coating system, tested per ASTM D2863-19. The synthesis is conducted in butyl cellosolve at 120°C under nitrogen, and the residual halohydrin is quenched with dilute NaOH to reduce hydrolyzable chloride below 100 ppm. Regulatory compliance requires IEC 61249-2-21 conformance for halogen content in printed circuit boards and WEEE status for end-of-life recyclability. For conventional applications where a UL 94 V-0 rating at 2.0 mm thickness is the primary specification, the bromothiazole-based hardener is loaded at 15 phr; when halogen-free status is mandated under IEC 61249-2-21, the adduct is capped at 2 phr to keep total bromine below 900 ppm. The downstream manufacturing process involves melt-blending the adduct with solid epoxy resin, leveling agent, and titanium dioxide on a twin-screw extruder with a L/D ratio of 40:1, followed by cryogenic grinding to a particle size distribution of D50 < 40 µm. The terminal products are electrostatic spray-grade powder coatings for steel office furniture and transformer housings, where the cured film must withstand salt spray exposure for 1,000 hours per ISO 9227.

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Certification & Compliance

Methyl 2-Amino-5-Bromo-1,3-Thiazole-4-Carboxylate 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

Methyl 2-amino-5-bromo-1,3-thiazole-4-carboxylate (CAS 145062-64-4) is a heterobifunctional thiazole intermediate supplied as an off-white to pale yellow crystalline powder. The product meets a purity specification of ≥97% by reverse-phase HPLC (C18, 5 µm, 250 × 4.6 mm column; UV detection at 254 nm, area normalization), with the major single impurities assigned to the 4-carboxylic acid hydrolysis product (≤1.5%) and a dibrominated side-product (≤0.8%). Molecular formula C₅H₅BrN₂O₂S corresponds to a molar mass of 237.07 g·mol⁻¹. The material is soluble in dimethyl sulfoxide (> 50 mg·mL⁻¹), dimethylformamide, and acetone, but exhibits limited aqueous solubility (<0.5 mg·mL⁻¹ at 25 °C). Storage is recommended under inert argon atmosphere at 0–6 °C in sealed, foil-wrapped containers; under these conditions lot-stability monitoring shows <1.8% loss of assay per annum and no measurable increase in the carboxylic acid impurity beyond the release limit over 24 months.

Where does Methyl 2-Amino-5-Bromo-1,3-Thiazole-4-Carboxylate fit in heterocyclic building block libraries?

The compound provides three orthogonal reactive sites that allow independent functionalisation without protecting group interplay. The 2-amino group undergoes acylation, sulfonylation, or reductive amination using standard protocols; condensation with activated carbonyl compounds yields fused bicyclic systems relevant to antibacterial and kinase-targeted scaffolds. The methyl ester at C‑4 can be hydrolyzed under mildly basic conditions (1 M LiOH, tetrahydrofuran/water, 0–5 °C, 3 h) or converted to primary amides, Weinreb amides, and hydrazides. The 5-bromo substituent is the key metalation handle, enabling Pd-catalyzed cross-coupling with boronic acids, pinacol boronates, organozinc reagents, and terminal alkynes. In a prototypical Suzuki–Miyaura sequence, the bromothiazole is coupled with 1.05 equiv of arylboronic acid using Pd(PPh₃)₄ (2 mol%) and Na₂CO₃ (2 M aq.) in 1,4-dioxane at 80 °C for 6–8 h, delivering 5-arylated products with isolated yields typically in the 72–89% range across a panel of electron-rich and electron-deficient aryl donors. The retention of the ester and free amine after coupling is preserved, as confirmed by ¹H NMR and LC-MS.

When Cross-Coupling Selectivity Determines Downstream Pharmacophore Success

In multi-step synthetic routes aimed at ATP-competitive kinase inhibitors or allosteric GPCR modulators, the presence of the 5-bromine atom imposes several boundary conditions not encountered with non-halogenated 2-aminothiazole-4-carboxylate esters. First, catalytic hydrogenolysis over Pd/C ( 10% w/w, H₂ balloon) rapidly cleaves the C–Br bond, leading to 2-amino-1,3-thiazole-4-carboxylate with <30 min half-life in ethanol at 25 °C. This mandates the use of non‑hydrogenative deprotection protocols (e.g., TFA-mediated Boc removal) whenever the bromide must be retained for a late-stage diversification. Second, the oxidative addition step in palladium-catalyzed couplings is acutely sensitive to the electronic character of the thiazole π‑system. With electron-poor 2‑aryl bromothiazoles, the rate of oxidative addition to Pd(0) is accelerated relative to phenyl bromide; comparative kinetic profiling by Buchwald’s group indicates that the thiazole core can raise the turnover frequency by a factor of 2–4 in amination reactions when measured against standard aryl bromide substrates (J. Am. Chem. Soc. 2003, 125, 6653). This heightened reactivity, while advantageous for cross-coupling efficiency, necessitates rigorous exclusion of moisture and oxygen to avoid protodebromination and catalyst deactivation. Third, the amino group can participate in off-cycle N‑arylation when attempted one‑pot sequences use excessive base or elevated temperatures, generating oligomeric material on pearl-scale batches. Consequently, reaction calorimetry data from kilo-lab campaigns shows that maintaining the internal temperature at ≤75 °C and limiting the free base to <2.5 equiv relative to the substrate suppresses the pathway to <1% of the mass balance.

Comparative Reactivity of Halogenated 2-Aminothiazole Esters

The choice of the 5‑bromo analogue over its 5‑chloro, 5‑iodo, or non‑halogenated congeners is dictated by a trade-off between oxidative addition kinetics, cost efficiency, and storage stability. The table below collates key molecular and reaction‑relevant properties across a set of methyl 2‑amino‑5‑X‑1,3‑thiazole‑4‑carboxylates.

Property	5-Br (target)	5-Cl	5-I	5-H
Molar mass (g·mol⁻¹)	237.07	192.62	284.07	158.18
Melting range (°C)	122–125	139–142	108–111 (dec.)	98–101
Typical purity (HPLC, % area)	≥97	≥97	≥95	≥98
Relative rate of oxidative addition (Br = 1.0)	1.0	0.04–0.08	1.2–1.5	n.a.
C–X bond dissociation energy (kJ·mol⁻¹)	285	350	218	n.a.
Storage stability (t₉₀ at 4 °C, sealed, argon)	24 months	36 months	8 months	48 months

Oxidative addition rates were estimated from competitive coupling experiments with Pd₂(dba)₃/XPhos catalytic system in toluene at 50 °C, following the protocol calibrated in J. Org. Chem. 2008, 73, 5073. The 5‑iodo derivative, while showing slightly faster oxidative addition, undergoes noticeable thermal debromination and homocoupling at ambient storage, which limits its utility in multi‑kilogram campaigns. The 5‑chloro analogue requires significantly harsher conditions ( >110 °C, dialkylbiarylphosphine ligands) for efficient cross-coupling, which exacerbates ester cleavage and amine oxidation.

Stability and Storage Under Manufacturing Conditions

The methyl ester group is susceptible to hydrolytic cleavage in the presence of water and catalytic acid or base. Forced degradation studies at 40 °C and 75% relative humidity without desiccant show 4.2% conversion to 2-amino-5-bromo-1,3-thiazole-4-carboxylic acid after 168 h. Therefore, bulk intermediate intended for multi-step synthesis is packaged under nitrogen with a moisture content below 0.5% (Karl Fischer titration, USP <921>). Pre‑drying of the solid at 40 °C under vacuum (<0.1 mbar) for 4 h immediately before use is required for moisture‑sensitive processes such as Weinreb amide formation or organozinc coupling. The melting endotherm measured by differential scanning calorimetry ( 5 K·min⁻¹, nitrogen) shows a sharp onset at 121.4 °C, and a decomposition exotherm initiates above 180 °C; this limits melt‑phase processing. Residual solvent specifications conform to ICH Q3C options for Class 2 and 3 solvents: total residual acetone ≤5000 ppm, DMF ≤880 ppm. No Class 1 solvents are employed in the current manufacturing process. Incoming QC protocols for Methyl 2-Amino-5-Bromo-1,3-Thiazole-4-Carboxylate typically apply a C18 narrow-bore column ( 2.1 × 100 mm, 1.7 µm) with a gradient of 0.1% formic acid in water and acetonitrile over 12 min. System suitability complies with USP <621>: retention time window 3.9–4.1 min, tailing factor ≤2.0, theoretical plates ≥25,000. The target impurity profile (Table) defines reporting, identification, and qualification thresholds aligned with ICH Q3A for a daily intake of ≤2 g/day.

Impurity	Relative retention	Specification (%)	Identification threshold (%)	Qualification threshold (%)
2-Amino-5-bromo-1,3-thiazole-4-carboxylic acid	0.32	≤1.5	0.10	0.15
Dibrominated analogue	1.18	≤0.8	0.10	0.15
Unspecified individual	–	≤0.10	0.10	0.15
Total impurities	–	≤3.0	–	–

The 5‑bromo compound can be unequivocally distinguished from the 5‑chloro analogue by the isotopic pattern observed in LC‑MS (M+H⁺ 237.9/239.9 for ⁷⁹Br/⁸¹Br, intensity ratio 1:1) and by the melting point depression of 12–17 °C relative to the 5‑Cl derivative. The amino proton signals appear as a broad singlet at 6.47 ppm in DMSO‑d₆, whereas the methyl ester displays a sharp three-proton singlet at 3.78 ppm. These spectroscopic fingerprints serve as routine identity checks and differentiate the target compound from its ring‑halogenated or ester‑exchanged variants without requiring extensive chromatographic method development.