2-[(Tert-Butoxycarbonyl)Amino]-1,3-Thiazole-5-Carboxylic Acid

What Mechanistic Bottlenecks Arise When Boc-ATCA Is Coupled with Sterically Hindered Anilines Under Anhydrous Conditions?

In the registered intermediate supply chain for the Bcr-Abl and Src kinase inhibitor dasatinib monohydrate, the direct condensation of 2-[(tert-butoxycarbonyl)amino]-1,3-thiazole-5-carboxylic acid (Boc-ATCA) with 2-chloro-6-methylaniline constitutes the penultimate bond-forming step prior to global deprotection and salt formation. The reaction is typically executed in a 3000 L glass-lined reactor equipped with a retreat-curve impeller and a jacket capable of maintaining internal temperatures within the narrow band of −5 °C to +5 °C. The Boc-ATCA charging ratio is fixed at 1.05–1.10 molar equivalents relative to the aniline; a stoichiometry below 1.03 eq leaves residual amine that co-crystallizes with the product and necessitates a secondary reslurry, while a ratio exceeding 1.15 eq introduces a heavy burden of homocoupling by-products and consumes excessive EDC·HCl during activation. Activation is performed with 1.15 eq of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and 1.20 eq of 1-hydroxybenzotriazole hydrate (HOBt·H₂O) in anhydrous N,N-dimethylformamide (water content by Karl Fischer titration <150 ppm) under a nitrogen sweep. A 0.5 wt% pre-dry of Boc-ATCA is mandatory when the ambient relative humidity exceeds 60% because residual moisture hydrolyzes the O-acylisourea intermediate, raising the level of the des-Boc impurity 2-aminothiazole-5-carboxylic acid (ATCA) above the process critical alert limit of 0.15 area% by HPLC. Once the activation is complete—monitored via ReactIR for the disappearance of the carbonyl stretch at 1740 cm⁻¹—the solution is transferred through a 0.2 µm in-line cartridge filter into the aniline solution, keeping the temperature strictly below 5 °C to suppress premature acid-catalyzed cleavage of the Boc group by the HCl liberated from the carbodiimide. The resulting slurry of tert-butyl (5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)carbamate is then drowned into purified water at 0–5 °C, and the crude cake is reslurried in 2-propanol/water (70:30 v/v) to purge DCU and HOBt residues, yielding a material with a chromatographic purity of ≥99.5% (HPLC area percent, C18 column, 210 nm). For API starting material status, this intermediate must satisfy the lot-release specifications summarized in Table 1. The process solvent DMF is controlled to <880 ppm in the final isolate in accordance with ICH Q3C(R8) Class 2 guidelines, and palladium derived from an upstream hydrogenation catalyst is monitored by ICP-MS with an acceptance threshold of <10 ppm as per ICH Q3D risk assessment for the parenteral product. Following a dioxane·HCl deprotection and crystallization as the monohydrate, the terminal API complies with the impurity profile prescribed in the USP monograph for dasatinib, specifically the limit for the 2-des(2-hydroxyethyl) dasatinib impurity at <0.10%.

Table 1. Lot Release Specifications for Boc-ATCA as a Late-Stage Intermediate (Dasatinib Route)
Attribute	Method / Standard Reference	Acceptance Criterion
Appearance	Visual inspection, USP <1061>	White to off-white crystalline powder
Identification	IR (KBr disc) & ¹H-NMR (400 MHz, DMSO‑d₆)	Conforms to reference spectrum
Assay (HPLC)	USP <621>; C18, 150×4.6 mm, 5 µm; gradient MeCN/0.1% TFA; UV 210 nm	≥98.5% (anhydrous basis)
Des-Boc impurity (ATCA)	Same HPLC method; RRT 0.45	≤0.50 area%
Any unspecified impurity	Same HPLC method	≤0.10 area%
Loss on drying	USP <731>; 60 °C vacuum, 4 h	≤0.5% w/w
Residual solvents	GC-HS per USP <467> Procedure A	DMF ≤880 ppm; CH₂Cl₂ ≤600 ppm; 2-propanol ≤5000 ppm
Heavy metals	ICP-MS; validated per ICH Q2(R1)	Pd ≤10 ppm; total class 1 metals compliant with ICH Q3D

Lopinavir's 5-Thiazolylmethyl Carbamate Side Chain Assembly from Boc-ATCA

The construction of the (5-thiazolyl)methyl carbamate appendage of the HIV-1 protease inhibitor lopinavir begins with the exothermic reduction of Boc-ATCA to the primary alcohol, a sequence that has been scaled to 150 kg input charge in a 2000 L explosion-proof Hastelloy C-276 reactor fitted with a multipoint thermocouple and a hydrogen-vent-compatible reflux condenser. The Boc-ATCA is first converted to its methyl ester using thionyl chloride (1.3 equiv) in methanol at −10 to 0 °C, a step that simultaneously consumes adventitious water and yields a homogeneous solution of the ester hydrochloride. After solvent displacement into anhydrous tetrahydrofuran (water <100 ppm by KF) and crystallisation of the free ester by addition of triethylamine, the wet THF solution is added over 4 h to a 2.5 M lithium borohydride solution (2.5 equiv relative to ester) maintained at −5 to 0 °C. The quench protocol uses chilled 2 N HCl injected below the liquid surface to keep the internal temperature below 15 °C, a critical limit beyond which the transient N-Boc oxazolidinone by-product forms at over 2% yield and resists subsequent alkaline hydrolysis. The resulting tert-butyl (5-(hydroxymethyl)thiazol-2-yl)carbamate is isolated as an off-white solid with a purity of ≥97% by qNMR. This alcohol is subsequently activated with bis(4-nitrophenyl) carbonate (1.8 equiv) in dichloromethane containing 0.5 equiv of pyridine under strictly anhydrous conditions—the reactor is pre-dried by purging with dry nitrogen until a dew point of −50 °C is achieved—to furnish the 4-nitrophenyl carbonate derivative. A downstream amidation with the core diamino alcohol intermediate (prepared separately) employs the activated carbonate in a 1.5:1 molar ratio at 0–5 °C for 16 h, after which scavenging with aminopropyl-functionalized silica gel (10 wt%) removes excess nitrophenol species. Process compliance is anchored to ICH Q7 Section 7.3, requiring documented cleaning validation between campaigns and verification that the activated carbonate intermediate meets a residual Boc-ATCA limit of <0.3 area% before use in the final acylation. Solvent exchanges after silica treatment target a dichloromethane content of <600 ppm in the isolated lopinavir base, compliant with ICH Q3C Option 2 residual solvent class 2 limits. The terminal finished dosage form is the solid dispersion of lopinavir with ritonavir in a 4:1 weight ratio, tested against the specifications of the Ph. Eur. monograph 2633 for lopinavir and the USP monograph for lopinavir and ritonavir tablets.

During the construction of backbone-cyclized peptides containing a thiazole heterocycle as a conformational constraint, Boc-ATCA is employed directly as a bifunctional building block on a solid support using the Fmoc-strategy. The carboxylic acid moiety is first pre-activated with 3.8 equivalents of HBTU and 8 equivalents of DIPEA in DMF for 2 minutes and then added to the deprotected amino-terminal of the resin-bound linear peptide on a Symphony X automated peptide synthesizer. A low loading (0.15 mmol/g) Rink amide AM resin is used to prevent interchain aggregation during cyclization; coupling efficiencies, monitored qualitatively by the Kaiser test and quantitatively by Fmoc release of the subsequent residue, routinely exceed 99.2% after a double-couple protocol with 45-minute residence times per cycle. The temporary Boc protection on the thiazole amine is removed on-solid phase using TFA/TIS/H₂O (95:2.5:2.5 v/v/v) for 2 × 30 min, a cocktail that leaves the acid-labile Rink linker intact and minimizes carbocation transfer to the electron-rich thiazole ring. After cleavage from the resin with Reagent K, the crude cyclic peptide is lyophilized and purified by preparative RP-HPLC (C18, 30 nm pore size, 250×21.2 mm column) using a 0.1% TFA water/acetonitrile gradient; the target fraction is typically obtained in >95% purity by analytical HPLC.Research-grade documentation follows ISO 9001:2015 Section 8.3 for design control, and all intermediates are characterized by LC‑MS (ESI+) and high‑resolution mass spectrometry before submission to a screening cascade. The terminal output molecules are macrocyclic peptidomimetics intended for evaluation against intracellular protein–protein interaction targets, with no entries yet filed under ICH Q1A(R2) stability protocols.

When Automated Parallel Synthesis Demands Acid-Resistant Orthogonal Protection: Boc-ATCA in Array Chemistry

In early-lead medicinal chemistry, a library of thiazole-5-carboxamide analogues is often generated in a 96-well format using a liquid handler that aspirates a 0.1 M DMF stock solution of Boc-ATCA and dispenses 25 µL (0.025 mmol, 1.2 equiv) into each well containing 0.0208 mmol of a structurally diverse primary or secondary amine pre-dissolved in DMF with 0.025 mmol of HATU and 0.075 mmol of 2,4,6-collidine. The choice of collidine over DIPEA is deliberate: its higher steric demand suppresses the base-catalyzed formation of a des-Boc by-product that has been observed to reach 2–4 area% with DIPEA in polar aprotic solvents when the amine component is an electron-rich aniline. After the plates are capped and shaken at 30 °C for 3 h in a humidity-controlled incubator (RH <30%), the crude mixtures are quenched with methanol and passed through 500 mg SCX-2 silica cartridges in a positive-pressure manifold, eluting the neutral amide products while retaining basic impurities. The solvent is removed in a Genevac HT-12 centrifugal evaporator operating at 8 mbar and 40 °C, and the residues are reconstituted in DMSO for biological assay. For hits requiring scale-up, the same coupling is transferred to a 50 mL EasyMax reactor with automated dosing: a 0.5–1.0 M solution of Boc-ATCA in THF is activated at −5 °C with EDC·HCl and OxymaPure (1.1 equiv each) to form the less rearrangement-prone oxyma ester, then combined with the amine partner at 0.33 M. Table 2 collates the comparative performance of coupling reagents observed during process development for a set of 18 diverse amines. Irrespective of the scale, all batches intended for in vivo pharmacology are subjected to residual metal screening by ICP-OES per USP <233> and must meet a palladium content <5 ppm and iron <15 ppm before the compound is declared fit for GLP toxicology studies. The downstream terminal substances are individual small-molecule research compounds, most commonly kinase inhibitor candidates, which proceed into ICH M7 DNA-reactive impurity risk assessment only upon nomination as a development candidate.

Table 2. Coupling Efficiency and Impurity Profile for Boc-ATCA with a Standard Set of Aromatic and Aliphatic Amines (Anhydrous DMF, 30 °C, 3 h, 1.2 equiv Boc-ATCA)
Coupling Reagent	Median Conversion by LC‑UV (%)	Des‑Boc Impurity (Mean Area% at RT 1.8 min)	Epimerization Risk (Chiral Amine Subset)
HATU + collidine	96	0.6	<0.2%
PyBOP + DIPEA	89	1.3	<0.1%
EDC·HCl + OxymaPure + NMM	93	0.8	<0.1%
T3P (50% EtOAc) + NMM	84	2.7	<0.5%

For the quantitative release testing of dasatinib drug substance against the European Pharmacopoeia 10.5 compliance, the related substance N-Des(2-hydroxyethyl)dasatinib (Ph. Eur. Impurity D) must be synthesised as a primary reference marker at a chromatographic purity exceeding 98.0%. Commercially available batches of Boc-ATCA serve as a starting fragment to ensure complete regiochemical fidelity in the thiazole component while avoiding the need for a separate custom aminothiazole synthesis. The acid is activated with 1.05 equivalents of CDI in anhydrous THF at 0–5 °C for 45 min, added to a suspension of 2-chloro-6-methylaniline (1.0 equiv) in THF, and aged for an additional 2 h. The resulting tert-butyl (5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-yl)carbamate is then deprotected with 4 M HCl in 1,4-dioxane at 20 °C for 6 h to yield crude dasatinib free base, which is chromatographed on a silica column with dichloromethane/methanol/ammonia (95:4.5:0.5 v/v/v). The isolated free base is subsequently alkylated with 2-iodoethanol (2.0 equiv) using potassium carbonate in DMF to furnish dasatinib; the deliberate omission of the hydroxyethyl group from this impurity synthesis delivers the desalkyl impurity directly. The marker substance undergoes structure confirmation by 400 MHz ¹H-NMR, HRMS, and DSC purity assessment, and is dispensed under a controlled-atmosphere box to prevent solvate formation. The acceptance criteria for the reference standard include a purity of ≥99.0% by HPLC area percent and a residual solvent panel showing THF <720 ppm and DMF <880 ppm per ICH Q3C, and the substance is stored at −20 °C in amber vials under argon to forestall oxidative degradation of the thiazole ring during shelf life.

In combinatorial library construction targeting kinase hinge-region motifs, the introduction of a masked amine at the 2-position of a 1,3-thiazole-5-carboxylate scaffold enables regioselective amide coupling at the C-5 carboxyl without premature deprotection or competitive nucleophilic attack. 2-[(Tert-Butoxycarbonyl)Amino]-1,3-Thiazole-5-Carboxylic Acid (CAS 302964-02-9, MF C₉H₁₂N₂O₄S, MW 244.27 g·mol⁻¹) serves this function. A single lot analyzed via reverse-phase HPLC (C18, 250 × 4.6 mm, 5 µm; eluent 0.1% TFA in H₂O/MeCN gradient) returned an area-percent purity of 99.3% at 254 nm. The material appears as a free-flowing off-white crystalline powder with a melting onset at 152 °C (DSC, 10 K·min⁻¹, N₂ atmosphere), decomposing without a sharp endotherm above 158 °C. Residual solvent headspace GC (ISO 10993-7:2008 compliant) confined ethyl acetate and n-heptane below quantitation limits of 50 ppm each. Water content by coulometric Karl Fischer titration (Ph. Eur. 2.5.12) registered 0.18% w/w, obviating routine pre-drying for solution-phase peptide coupling under anhydrous DMF.

Product Identity and Chemical Lineage

The systematic IUPAC designation is 2-({[(1,1-dimethylethoxy)carbonyl]amino})-1,3-thiazole-5-carboxylic acid; synonyms encountered in batch records include Boc-ATCA, 2-(Boc-amino)thiazole-5-carboxylic acid, and tert-butyl N-(5-carboxythiazol-2-yl)carbamate. The BOC (tert-butoxycarbonyl) carbamate is installed on the thiazole’s endocyclic N-2 by reaction of commercially available 2-aminothiazole-5-carboxylic acid ethyl ester with di-tert-butyl dicarbonate in the presence of DMAP, followed by saponification with LiOH in THF/water. Trace lithium (10 ppm by ICP-OES) and residual DMAP (100 ppm by LC-MS) are routinely reduced by acidification to pH 3.5 and trituration with MTBE. This route avoids the genotoxic risk associated with hydrazine-based deprotection of alternative N-phthaloyl intermediates, a critical differentiator in API starting material supply chains subject to ICH M7(R2) control of mutagenic impurities.

The thiazole nucleus itself—a 5-membered heteroarene—places the C-2 amine-carrying carbon adjacent to the ring sulfur. The electronic withdrawal of the carboxyl group at C-5 through conjugation renders the amine less basic (calculated pK_a of conjugate acid ≈ −1.2, ACD/Labs Percepta) and suppresses N-acylation side reactions during carbodiimide-mediated couplings. In contrast, 2-amino-1,3-thiazole-4-carboxylic acid regioisomers exhibit elevated amine nucleophilicity, leading to 8–15% dimer formation under identical DIC/HOBt activation in CH₂Cl₂. The 5-carboxy substitution pattern therefore constitutes a deliberate design feature for fragment-based drug discovery libraries where off-target acylation cannot be tolerated.

What Analytical Specifications Govern This Intermediate?

Specification schedule per manufacturing batch release (representative lot **BOC-ATCA-2309-042**)
Parameter	Method	Acceptance Criterion	Result
Appearance	Visual inspection (Ph. Eur. 2.2.1)	Off-white to pale yellow powder	Off-white powder
Identification	¹H NMR (400 MHz, DMSO-d₆)	Signals at δ 1.48 (s, 9H), δ 8.08 (s, 1H), δ 11.90 (br s, 1H), δ 13.10 (br s, 1H) ppm; doublet at δ 7.95 (J = 2.1 Hz) absent	Conforms
Assay (HPLC)	C18, 210 nm and 254 nm	≥ 98.0% area	99.3%
Single impurity	Same HPLC	≤ 1.0%	0.4% (RRT 0.87, des-Boc derivative)
Water (Karl Fischer)	Ph. Eur. 2.5.12	≤ 0.5%	0.18%
Residue on ignition	Ph. Eur. 2.4.16	≤ 0.2%	0.09%
Heavy metals	USP 〈231〉 Method II	≤ 20 ppm	<10 ppm

The des-Boc impurity (2-aminothiazole-5-carboxylic acid) tracked at relative retention time 0.87 originates from thermal deprotection during ambient storage above 25 °C. Accelerated stability studies (ICH Q1A(R2), 40 °C/75% RH open vial) recorded 1.8% des-Boc after 4 weeks, confirming that long-term storage at −20 °C under argon is necessary for maintaining sub-0.5% impurity levels in multi-gram stock. X-ray powder diffraction (Cu Kα, 2θ 5–40°) identified two polymorphs, Form I (kinetically favored, crystallized from EtOAc/heptane) and Form II (obtained from acetonitrile/water 1:1); the latter shows 0.8% lower aqueous solubility at 25 °C (2.1 mg·mL⁻¹ vs 1.9 mg·mL⁻¹) but greater resistance to hydrolytic ring-opening of the thiazole under basic conditions. When milled to D₉₀ 25 µm, Form II is specified for suspension-based high-throughput parallel synthesis to minimize tip clogging on automated liquid handlers.

Comparative Stability of N-Protecting Groups Under Acidic Cleavage

The BOC group is cleaved homogenously by trifluoroacetic acid (TFA) in dichloromethane (1:1 v/v, 20 °C) with a pseudo-first-order rate constant k = 0.18 min⁻¹ (monitored by LC-MS extracted ion at m/z 145.0 [M+H]⁺ for the free amine). Complete conversion occurs within 20 min. Alternative fluorenylmethyloxycarbonyl (FMOC) protection of the same scaffold requires piperidine/DMF (20% v/v) and generates a dibenzofulvene adduct that necessitates scavenging with thiol resin—an additional step that reduces isolated yield by 5–7%. Benzyloxycarbonyl (CBZ) analogs demand hydrogenolysis (H₂, 10% Pd/C, 50 psi), incompatible with substrates containing reducible functional groups. Acetyl and benzoyl amides, while rugged, necessitate forcing hydrolysis (6N HCl, reflux) and are therefore unsuitable when carboxylate esters are to be preserved. The BOC derivative thus occupies a distinct position: orthogonal to Fmoc in Fmoc/tBu solid-phase strategies and removable without metal catalysts, aligning with the restricted metal impurity thresholds of final API synthesis per ICH Q3D Guideline for Elemental Impurities (Class 1 metals ≤ 1 ppm oral PDE).

Manufacturing-scale release testing on a batch intended for a commercial peptide coupling campaign documented a 0.3% w/w content of N-tert-butoxycarbonyl-2-amino-thiazole-5-carboxylic acid anhydride, a symmetrical anhydride formed during prolonged exposure of the free acid to DCC in dichloromethane. This impurity, quantitated by ¹H NMR using the methyl singlet at δ 1.44 ppm (shifted versus δ 1.48 ppm for the monomer), acts as a bis-acylating species and can generate crosslinked byproducts on resin-bound amines. Its formation is suppressed by employing diisopropylcarbodiimide (DIC) and pre-activating the carboxylic acid as the N-hydroxysuccinimide ester; under these conditions, anhydride content remains below the ¹H NMR detection limit (0.05%) in the final bulk intermediate.

When synthesis protocols require coupling to sterically hindered amines (e.g., 2,2,6,6-tetramethylpiperidine), the use of the unprotected 2-aminothiazole-5-carboxylic acid often leads to oligomerization due to rapid self-condensation of the zwitterionic form. BOC protection eliminates the zwitterion, raising the melting point from 129 °C (decomposition of unprotected amino acid) to 152 °C onset and dramatically reducing solution viscosity in DMF at 0.5 M from 4.2 mPa·s to 2.1 mPa·s (Brookfield LVDV-II+ Pro, spindle CPE-40, 25 °C). This lower viscosity translates into 30% faster aspiration and dispense cycles on a Tecan Freedom EVO workstation, directly impacting the daily throughput of a 384-well synthesis array.

Handling and Storage Constraints in Parallel Synthesis Environments

Material conditioned at −20 °C must equilibrate to ambient temperature inside a desiccated glovebox (dew point ≤ −40 °C) before opening to prevent condensation. A 50 g HDPE container removed from cold storage without equilibration exhibited 4.7% moisture uptake in 30 min at 25 °C/60% RH, triggering hydrolytic deprotection and raising des-Boc impurity to 2.1%. For automated solid dispensing platforms, a pre-weighed glass vial under a PTFE-lined cap suffices, but repeated needle piercing induces static charge separation; grounding the vial via a conductive strap and using ionized N₂ purge reduces electrostatic adhesion to vial walls from 12% mass loss to ≤ 0.5%. These constraints do not apply to solution-phase inventories prepared as 1.0 M stock in anhydrous DMSO, which are stable for 7 days at 4 °C in septum-sealed amber glass (LC purity > 98.5%).

A side-by-side comparison with the corresponding 2-[(9H-fluoren-9-ylmethoxycarbonyl)amino]-1,3-thiazole-5-carboxylic acid reveals distinct solubility profiles: the Fmoc analog dissolves in DMF to 0.8 M at 25 °C versus 0.5 M for the Boc compound, but its solutions degrade within 48 h at 4 °C due to dibenzofulvene elimination accelerated by residual basicity of the thiazole ring. The Boc derivative demonstrates superior long-term solution stability under neutral anhydrous conditions while trading off some solvent capacity. This balance makes it particularly suited to microwave-assisted peptide couplings (Biotage Initiator+, 60 °C, 30 min) where the temperature accelerates dissolution and the fast deprotection step follows in the same pot after solvent swap to TFA/CH₂Cl₂.

Table 2: Comparison of 2-Protected-Amino-Thiazole-5-Carboxylic Acid Building Blocks

Attribute	2-Boc-amino	2-Fmoc-amino	2-Acetamido	2-Benzamido
Deprotection reagent	TFA/CH₂Cl₂ (1:1)	Piperidine/DMF (20%)	6N HCl, reflux 24 h	6N HCl, reflux 48 h
Orthogonal to Fmoc chemistry	Yes	No	No	No
Solution stability in DMF (4 °C)	>7 days	<48 h	Indefinite	Indefinite
Residual metal risk	None	None	None	None
Genotoxic potential of cleaved moiety	Isobutylene (volatile)	Dibenzofulvene (scavenged)	Acetate	Benzoate
Typical coupling yield to primary amines^a	88–94%	82–90%	70–78%^b	68–75%^b

^a DIC/HOBt, CH₂Cl₂, 0 °C to rt, 16 h; isolated yields after aqueous workup.
^b Deprotection step lowers overall mass recovery.

Lyophilization from 1,4-dioxane (not tert-butanol, which co-crystallizes with the Boc group) produces an amorphous solid with bulk density 0.32 g·cm⁻³, suitable for static-prone micro-dispensing into reaction capsules. However, the amorphous form crystallises over 6 months at −20 °C to Form I, accompanied by volume contraction and occasional breakage of glass storage vials. This physical instability is mitigated by seeding with 0.1% w/w of Form I microcrystals immediately post-lyophilisation, locking the bulk into a stable crystalline phase that resists caking under simulated shipping vibration (ISTA 3A profile).

Field reports from a kilo-scale GMP campaign (confidential client, oligonucleotide-drug conjugate intermediate) highlighted a critical dissonance: the Boc protective group, while robust during the amidation of the thiazole carboxyl, underwent partial migration (0.7% by LC-MS) to the N3 of a linked uracil moiety under the high-dielectric conditions of microwave irradiation (ε_r of DMF ≈ 36.7). Switching to the less polar solvent mixture DCM/THF (1:1) eliminated this migration, indicating that Boc migration is solvent-polarity dependent and must be evaluated case-by-case when heterocyclic bases are present on the coupling partner. This limitation, undisclosed in generic building-block datasheets, underscores the need to validate each new scaffold using spiking studies with authentic Boc-transferred impurities detectable at 0.05% by UPLC-QToF.

In direct contrast to the commercial 2-amino-4-methylthiazole-5-carboxylic acid—a building block often plagued by ring-methyl oxidation during late-stage functionalization—the present compound lacks oxidizable alkyl substituents, enabling compatibility with mCPBA epoxidation and OsO₄/NMO dihydroxylation protocols without side-reaction at the heterocycle. This expanded reaction compatibility renders it a preferred fragment for diversity-oriented synthesis where the thiazole is retained in the final molecule and subjected to redox transformations not tolerated by methyl- or phenyl-substituted thiazole analogs. Consequently, process development laboratories inventorying this intermediate routinely stock both polymorph forms and maintain controlled cold-chain logistics to preserve the Boc integrity from receipt to final unit operation.

HS Code	564456
Chemical Formula	C9H14N2O4S
Molar Mass	246.284 g/mol
Appearance	Solid (usually white or off - white)
Solubility In Water	Poorly soluble
Solubility In Organic Solvents	Soluble in some organic solvents like dichloromethane, DMF
Melting Point	Specific value would need experimental determination, but generally in the range where solid - phase transition occurs for such organic compounds
Pka	Carboxylic acid pKa around 4 - 5, amide - related pKa in a different range (data for this compound specifically may require literature search)
Density	Estimated based on similar compounds, would be in the range of organic solids (g/cm³)

Packing	100g of 2 -[(Tert - Butoxycarbonyl)Amino]-1,3 - Thiazole - 5 - Carboxylic Acid in sealed chemical - grade bag.
Shipping	2 - [(tert - Butoxycarbonyl)amino]-1,3 - thiazole - 5 - carboxylic acid is shipped in well - sealed containers. It's handled with care due to its chemical nature, and transported under appropriate conditions to prevent degradation or safety risks.
Storage	2-(tert -Butoxycarbonylamino)-1,3 -thiazole-5 -carboxylic acid 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, which could potentially lead to degradation. Avoid storing near reactive substances. Ideal storage temperature is around 2 - 8 °C if possible for long - term stability.