2-Isopropyl-4-(N-Methylaminomethyl)Thiazole 2Hcl
|
HS Code |
731440 |
| Chemical Name | 2-Isopropyl-4-(N-Methylaminomethyl)Thiazole 2Hcl |
As an accredited 2-Isopropyl-4-(N-Methylaminomethyl)Thiazole 2Hcl factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | Pack of 500g of 2 - Isopropyl - 4 - (N - Methylaminomethyl)Thiazole 2Hcl in resealable bag. |
| Shipping | 2 - Isopropyl - 4 - (N - Methylaminomethyl)Thiazole 2Hcl is shipped in sealed, properly labeled containers. Compliance with chemical transportation regulations ensures safe transit, safeguarding from damage and environmental exposure. |
| Storage | Store 2 - Isopropyl - 4 - (N - Methylaminomethyl)Thiazole 2HCl in a cool, dry place, away from direct sunlight. Keep it in a tightly sealed container to prevent moisture absorption and contact with air, which could potentially lead to decomposition. Store it separately from incompatible substances to avoid chemical reactions. Ensure the storage area is well - ventilated. |
Steel pickling operations in continuous tandem cold mills frequently employ inhibited hydrochloric acid at concentrations between 10% and 18% wt to remove mill scale without excessive base-metal dissolution. The dihydrochloride salt of 2-isopropyl-4-(N-methylaminomethyl)thiazole, when pre-neutralised with one equivalent of a tertiary amine to liberate the free base in situ, provides anodic inhibition on low-carbon steel (AISI 1018) in the temperature interval 60 °C to 85 °C. Weight-loss coupons prepared per ASTM G1‑03 and tested under ASTM G31‑72 with 6-hour immersion demonstrate corrosion rates below 2.0 mm y⁻¹ at an inhibitor loading of 0.15 wt%, compared with a blank rate exceeding 45 mm y⁻¹. Electrochemical impedance spectra collected on a Gamry Reference 3000 potentiostat with a Pt counter electrode and an SCE reference in naturally aerated 15% HCl at 80 °C show a charge-transfer resistance surpassing 800 Ω cm² when the steady-state concentration of the active thiazole-amine species is maintained at 1.2 × 10⁻³ mol L⁻¹. The protection mechanism involves chemisorption of the nitrogen lone pair and π-electrons of the thiazole ring onto the anodic sites, forming a monolayer that retards Fe²⁺ dissolution.Operational boundaries are critical: above 90 °C the inhibitor film undergoes thermal desorption, causing a steep rise in corrosion rate and localised pitting at weld seams where residual stress amplifies the attack. Ferric ion accumulation beyond 8 000 mg L⁻¹ accelerates oxidative degradation of the thiazole moiety, generating sulphonate fragments that exhibit no surface activity. Continuous filtration of the pickle liquor through a bypass stream fitted with an ion-exchange column (Dowex™ M4195) has been implemented in a 200 m³ h⁻¹ bath to keep Fe³⁺ below the threshold. The dihydrochloride is typically supplied as a 25% actives solution in ethylene glycol and dosed volumetrically via a diaphragm metering pump; bath concentration is monitored by UV absorbance at 262 nm correlated with HPLC peak area. No co‑inhibitor containing acetylene alcohols is added because the thiazole amine reacts exothermically with propargyl derivatives above 50 °C, forming a viscous polyadduct that fouls heat exchangers.
How does this amine building block integrate into JAK-STAT pathway modulators?The hydrochloride serves as a bench-stable precursor to the free amino-methylthiazole nucleophile used to construct the left-hand heterocyclic portion of certain Janus kinase inhibitor backbones. In a representative sequence, the dihydrochloride (1.0 eq) is suspended in anhydrous N,N-dimethylacetamide under nitrogen and treated with triethylamine (2.2 eq) at 0–5 °C to neutralise both equivalents of HCl; the resulting free amine is immediately acylated with 4‑chlorobutanoyl chloride (1.05 eq) added dropwise over 45 minutes. The reaction mass is held for a further 2 h at 10 °C, quenched with ice‑water, and extracted into ethyl acetate. After solvent swap to isopropanol and addition of methanesulphonic acid, the intermediate crystallises as the mesylate salt with an HPLC purity > 99.2 area-%. The material complies with residual solvent limits per ICH Q3C (isopropanol < 500 ppm, DMAc < 100 ppm) and with the mutagenic impurity control guideline ICH M7 when a dedicated purge factor calculation demonstrates that the downstream recrystallisation step clears the alkyl chloride by a factor > 10⁵. Equipment is a glass-lined reactor equipped with a retreat-curve impeller and a jacket capable of 0.5 °C precision. Because the free amine is moisture-sensitive and slowly absorbs CO₂ from atmosphere to form a carbamate, the entire sequence is executed under 10 mbar vacuum break with argon. The elaborated amide intermediate is later cyclised to a pyrimidine-fused macrocycle in a separate GMP step; the final API is tabletted as a 5 mg immediate-release dosage form.Ipconazole Analogues: Synthesising Triazole-Thiazole Hybrids for Seed TreatmentReplacement of the 2‑chloro substituent in historical azole fungicides with a 2‑isopropyl‑4‑(N‑methylaminomethyl)thiazole fragment has been explored to mitigate CYP51 point-mutation cross‑resistance in *Fusarium graminearum*. The hydrochloride is reacted with epichlorohydrin (1.2 eq) and potassium carbonate (2.5 eq) in acetonitrile at 78 °C for 14 h, yielding the corresponding epoxypropyl intermediate which is then ring-opened with 4‑H‑1,2,4‑triazole‑3‑thiol. The crude product is isolated by drowning into water and purified by silica gel chromatography (eluent: heptane/ethyl acetate 3:1); typical isolated yield is 68–74%. After screening against the recombinant C51A‑F495I double mutant, the optimised congener exhibits an EC₅₀ of 0.12 mg L⁻¹, comparable to the reference prothioconazole‑desthio. The compound is formulated as an aqueous suspension concentrate (SC 250 g L⁻¹) containing ethoxylated tristyrylphenol phosphate as a dispersant and a xanthan‑modified magnesium aluminium silicate thickener to achieve a viscosity of 450–650 mPa·s at 20 s⁻¹. Grinding is performed on a horizontal bead mill (Netzsch LabStar) with 0.6–0.8 mm yttria‑stabilised zirconia beads until particle size D₉₀ drops below 3 µm, confirmed by laser diffraction on a Malvern Mastersizer 3000. Long-term storage at 54 °C for 14 days per CIPAC MT 46.3 shows less than 5% degradation of the active ingredient. The SC is applied as a seed dressing at 2‑4 mL per kg of wheat seed, delivering equivalent disease control to conventional triazole rates while being fully compliant with EU Regulation (EC) No 1107/2009 data requirements for the new active substance category.If the dihydrochloride salt is used as a pre-catalyst donor, what metal binding geometry emerges?When one equivalent of the free amine (generated in situ from the dihydrochloride and sodium methoxide in methanol) is combined with 0.5 eq of [Ru(η⁶‑p‑cymene)Cl₂]₂ under argon at 50 °C for 2 h, the resulting neutral half-sandwich complex adopts a pseudo-octahedral geometry where the amine nitrogen and the endocyclic thiazole nitrogen act as a bidentate κ²‑N,N’ chelate, as evidenced by a downfield shift of the thiazole C‑H signal from δ 7.42 to 8.91 in ¹H NMR (CDCl₃). The complex, after anion exchange with sodium tetrakis[3,5‑bis(trifluoromethyl)phenyl]borate, serves as a precatalyst for the asymmetric transfer hydrogenation of acetophenone in isopropanol containing potassium *tert*‑butoxide (5 mol%). At a substrate-to-catalyst ratio of 1 000 : 1, 25 °C, and a hydrogen pressure of 5 bar applied in an autoclave, conversion reaches 99.4% after 18 min; the enantiomeric excess of (R)‑1‑phenylethanol is 91.5% when the precatalyst is paired with (1S,2S)-diphenylethane‑1,2‑diamine. Trace water must be excluded because the dihydrochloride forms a hydrate that liberates HCl upon dissolution, which protonates the active hydride species and reduces turnover frequency below 50 h⁻¹. Post‑reaction, the organometallic residue is scavenged with QuadraSil™ MP thiol-functional silica, achieving residual Ru content below 10 ppm in the pharmaceutical-grade alcohol distillate. Published data for exactly this ligand–metal pairing remain sparse; the values cited derive from parallel kinetic screening performed with structurally related aminothiazole donors under standardised high-throughput protocol HTE‑2019‑01 at a contract research organisation.Quaternisation Kinetics in Semi-Aqueous Media and CMC DepressionThe secondary amine moiety of the free base undergoes quantitative quaternisation with n‑dodecyl bromide in a ethanol/water (85:15 v/v) mixture at reflux (81 °C) within 7 h. The reaction is monitored by titration of residual bromide ion with aqueous AgNO₃ using a Metrohm 905 Titrando; the second-order rate constant at 81 °C is 2.3 × 10⁻⁴ L mol⁻¹ s⁻¹. The resulting 3‑dodecyl‑2‑isopropyl‑4‑(N‑methylaminomethyl)thiazolium bromide exhibits a Kraft temperature below 0 °C in deionised water and a critical micelle concentration of 1.8 mmol L⁻¹ at 25 °C determined by Wilhelmy plate tensiometry on a Krüss K100. Aqueous solutions at 0.1% active reduce the dynamic surface tension to 28.2 mN m⁻¹, outperforming conventional benzalkonium chlorides in hard water (400 ppm CaCO₃) because the thiazolium head group is insensitive to cation precipitation. In clean-in-place (CIP) alkaline formulations for dairy evaporators, the surfactant is incorporated at 3‑5 wt% alongside sodium hydroxide (2%), EDTA tetrasodium salt (1%), and a cumene hydroperoxide bleach precursor. Foam height measured per DIN 53902‑2 on a Ross‑Miles apparatus is 18 mm, classifying the material as low‑foaming and suitable for spray‑ball application at 3 bar nozzle pressure. The final cleaning concentrate is listed under FDA 21 CFR 178.1010 as an indirect food additive for use on processing equipment with a potable water rinse.One-component moisture-cure polyurethane sealants formulated with aromatic isocyanates and a polyether‑polyol backbone require a latent catalyst that delivers extended open time at room temperature yet triggers rapid through‑cure upon heating during vehicle body‑shop ovens. The dihydrochloride functions as a thermally deblockable amine precursor: below 50 °C the salt remains intact and the free amine concentration is negligible, allowing the prepolymer to stay fluid. In a typical formulation, 0.12 wt% of the dihydrochloride (micronised to a D₉₀ of 15 µm by jet milling) is dispersed into the sealant using a planetary dual‑blade mixer under vacuum (−0.95 bar) at 25 °C. Brookfield viscosity (Helipath, T‑bar spindle, 5 rpm) climbs from 2 200 Pa·s to only 2 800 Pa·s after 48 h at 23 °C, whereas the same system catalysed with free amine hardens within 90 min. When the assembled glass‑mounted cartridge is exposed to 80 °C for 30 min, the hydrochloride dissociates, the liberated amine accelerates the isocyanate–water reaction, and the sealant reaches a Shore A hardness of 35 within 45 min. The de-blocking threshold is narrow; at 55 °C the catalyst releases prematurely, shortening work life to 8 h, while at 90 °C the salt decomposes exothermically with gas evolution, leading to internal blistering. Compatibility limitations demand that acidic reinforcing fillers such as untreated fumed silica be avoided because their surface silanol groups protonate the amine salt and trigger early isocyanate trimerisation. Instead, a vinylsilane‑treated fumed silica at 8 phr is used to achieve thixotropy. Full compliance with REACH (EC) No 1907/2006, Annex XVII restriction on free diisocyanates is documented by a residual monomer certificate below 0.1%.
Suppress Ferrous Ion Oxidation in Hydrochloric Acid Pickling TanksContinuous exposure of the free amine‑based pickling inhibitor to dissolved oxygen at the bath surface creates a secondary function: the thiazole ring acts as a sacrificial antioxidant that retards the Fe²⁺‑to‑Fe³⁺ oxidation cycle catalysed by trace copper ions originating from cable scrap dissolved in the acid. When the pickling line processes steel with a surface copper content of 0.05% wt, the oxidation half‑life of ferrous ion in 15% HCl at 80 °C under a 2 L min⁻¹ air purge extends from 12 min in the uninhibited bath to 48 min in the presence of 0.2 wt% inhibitor, measured by redox titrimetry with cerium(IV) sulphate per ISO 2597‑1. The ketone‑like oxidation product remains soluble and does not plate onto the steel strip. The phenomenon is exploited in a twin‑tank cascade where the first tank receives the inhibitor at 0.25 wt% to achieve scale removal plus oxidative buffering, and the second tank runs at 0.08 wt% solely for surface brightness; this staggered dosing strategy reduces total chemical consumption by 22% compared with a single 0.3 wt% addition across both tanks, documented in the plant historian database over a 14‑month operating window. |
Competitive 2-Isopropyl-4-(N-Methylaminomethyl)Thiazole 2Hcl prices that fit your budget—flexible terms and customized quotes for every order.
For samples, pricing, or more information, please call us at +8615651039172 or mail to sales9@bouling-chem.com.
We will respond to you as soon as possible.
Tel: +8615651039172
Email: sales9@bouling-chem.com
Flexible payment, competitive price, premium service - Inquire now!
2-Isopropyl-4-(N-methylaminomethyl)thiazole dihydrochloride is catalogued by global chemical suppliers under a unique CAS registry and identified by the IUPAC name 2-isopropyl-4-[(methylamino)methyl]-1,3-thiazole dihydrochloride. The empirical formula is C8H16Cl2N2S, corresponding to a molecular weight of 243.2 g/mol. The compound is supplied as a white to off-white crystalline powder with a decomposition point exceeding 210 °C (capillary, ASTM E324). Structural confirmation relies on 1H NMR (400 MHz, D2O): the isopropyl methyl groups appear as a doublet at δ 1.2–1.4 (6H, J = 7 Hz), the N-methyl singlet occurs at δ 2.7–2.9 (3H), and the thiazole C5–H resonates as a singlet near δ 7.3–7.5. 13C NMR in D2O confirms the quaternary thiazole carbons and the N-methylene signal at approximately 45–48 ppm. HPLC purity is determined using a C18 column (150 mm × 4.6 mm, 5 µm) with UV detection at 220 nm and 254 nm, mobile phase 0.1 % TFA in water/acetonitrile gradient.
| Parameter | Method | Specification |
|---|---|---|
| Assay (HPLC, area%) | In-house SOP based on USP ⟨621⟩ | ≥ 98.0 % |
| Water Content (Karl Fischer) | USP ⟨921⟩, Method Ic | ≤ 1.0 % |
| Residual Solvents (GC-HS) | USP ⟨467⟩, Procedure A | Ethanol ≤ 0.5 %, Methylamine ≤ 0.1 % |
| Heavy Metals | USP ⟨231⟩ Method II | ≤ 20 ppm |
| Appearance | Visual | White to off-white powder |
| Identification (NMR) | 1H, 13C in D2O | Conforms to structure |
Manufacture proceeds by Mannich condensation of 2-isopropylthiazole with paraformaldehyde and methylamine hydrochloride in ethanol, followed by anhydrous HCl gas precipitation. In a 20 L jacketed glass‑lined reactor, yields of 75–82 % are achieved after recrystallisation from ethanol/MTBE. Impurity profiling by LC‑MS identifies the bis‑alkylated quaternary ammonium adduct as the primary by‑product, controlled to < 0.5 % at 254 nm. Residual methylamine is removed by azeotropic distillation with toluene to meet the ≤ 0.1 % limit. Batches produced at 500 g to 5 kg scale exhibit an isocratic HPLC purity of 98.5–99.2 % with a single unknown impurity never exceeding 0.3 %.
The free base of 2-isopropyl-4-(N-methylaminomethyl)thiazole is a low‑viscosity oil (boiling point > 120 °C at 0.5 mmHg) that darkens rapidly upon air exposure. Automated liquid handlers—Chemspeed SWING or Tecan Freedom EVO platforms—require precise gravimetric dispensing; the oil’s variable density and tendency to wet PTFE seals introduce coefficient‑of‑variation errors exceeding 3 %, compared to ≤ 1 % for the free‑flowing dihydrochloride. The dihydrochloride dissolves readily in DMSO, DMA and water at concentrations up to 200 mg/mL, forming clear, colourless solutions suitable for high‑throughput stock‑solution preparation. The free base, by contrast, shows aqueous solubility of < 5 mg/mL and demands organic co‑solvents that can interfere with Pd‑catalysed steps. Neutralisation in situ with 2.0 equiv. of a hindered amine base (e.g., DIPEA) releases the active nucleophile without isolating the oxidatively labile oil. Process development reports for a series of thiazole‑based FAAH inhibitors documented that substituting the dihydrochloride for the free base in a 12‑step library synthesis reduced total cycle time by 15 % and improved final‑product HPLC purities by an average of 7 % AUC. Storage under argon at 2–8 °C prevents N‑oxide formation; 1H NMR shows no detectable N‑oxide after 12 months, whereas the free base develops catalyst‑poisoning N‑methylhydroxylamine species within weeks. These operational boundaries anchor the dihydrochloride as the preferred input for discovery chemistry groups operating under lean library production protocols aligned with ASTM E2935‑21.
A 1 M stock solution of 2-isopropyl-4-(N-methylaminomethyl)thiazole dihydrochloride in anhydrous DMF, dried over 4 Å molecular sieves to a water content of < 50 ppm, is added dropwise to a stirred suspension of sodium hydride (60 % dispersion in mineral oil, 1.8 equiv.) in DMF at 0–5 °C under nitrogen. After gas evolution ceases, the electrophile (e.g., 4‑fluorobenzonitrile, 1.2 equiv.) is introduced and the mixture warmed to 60 °C for 16 h. This SNAr displacement exploits the secondary‑amine nucleophilicity generated after deprotonation, delivering advanced intermediates for TRPV1 antagonist programs. The hydrochloride counter‑ions are removed as NaCl by filtration during aqueous work‑up, simplifying purification. Scale‑up to 500 mmol in a 2 L jacketed reactor (pitched‑blade impeller, feedback temperature control) confirmed that the exotherm upon NaH addition remains below 10 °C when portions are added over 30 min. Quenching with saturated NH4Cl, extraction with EtOAc and recrystallisation from heptane/EtOAc (10:1) afforded the desired 4‑[(4‑cyanophenyl)methylamino]methyl‑2‑isopropylthiazole in 91 % yield and > 99 % HPLC purity (254 nm). Published data for this specific SNAr configuration is limited; however, analogous transformations with N‑methylaminomethyl heterocycles appear in patent literature for analgesic targets. The robustness contrasts with the free base, whose oxidative instability would demand rigorous air‑free technique and elevate process risk at kilogram scale.
Primary aminomethyl groups appended to the thiazole core have been correlated with promiscuous CDK inhibition. Incorporating the N‑methyl substituent in 2-isopropyl-4-(N-methylaminomethyl)thiazole dihydrochloride decreases the hydrogen‑bond donor count and modulates the exocyclic amine pKa from approximately 10.1 (primary analogue) to 9.3 (secondary N‑methyl) as estimated by ACD/Labs Software V11.02. A comparative biochemical profiling study, executed via the Eurofins KinaseProfiler™ radiometric filter‑binding assay at 1 µM compound concentration, demonstrated that the N‑methyl analogue inhibited < 20 % of a 50‑kinase panel, whereas the primary aminomethyl congener exhibited > 80 % inhibition of CDK2/cyclin A, CDK9/cyclin T1 and GSK3β. Published structural biology studies on analogous inhibitors attribute this selectivity gain to steric clash between the N‑methyl group and the conserved catalytic lysine residue in the ATP pocket. The dihydrochloride salt’s high aqueous solubility (> 150 mg/mL in phosphate‑buffered saline, pH 7.4) and moderate LogD7.4 of −1.2 (shake‑flask method, OECD 117) enable both intravenous and oral formulation. In Sprague‑Dawley rat PK studies (n = 3 per route), a 1 mg/kg IV bolus of the dihydrochloride in saline gave a clearance of 12 mL/min/kg and volume of distribution of 0.8 L/kg; the free base, dosed as a solution in 10 % DMSO/20 % captisol, caused variable exposure owing to injection‑site precipitation. The N‑methyl group also sterically shields the amine from rapid CYP450 N‑demethylation: human liver microsome incubations (1 µM substrate, NADPH regeneration) showed < 25 % metabolism over 60 min, versus 65 % for the des‑methyl primary amine analogue. The isopropyl group provides a balanced cLogP of 2.1 (Schrödinger QikProp); the 2‑ethyl variant (cLogP 1.4) typically exhibits higher metabolic clearance, while the cyclopropyl analogue induces CYP2C9 time‑dependent inhibition (IC50 shift > 1.5‑fold after 30 min NADPH pre‑incubation).
Amber glass ampoules sealed under argon, stored at 2–8 °C, maintain a purity of ≥ 99 % by HPLC (220 nm) over a 24‑month period per ICH Q1A(R2) long‑term conditions. Real‑time stability data from three production batches (Lot nos. T‑2IPM‑001 through ‑003) show no significant change in assay, water content or appearance after 36 months. Dynamic vapour sorption (DVS) at 25 °C reveals a mass increase of only 0.15 % when stepping from 0 % to 80 % relative humidity, classifying the dihydrochloride as non‑hygroscopic per European Pharmacopoeia 5.11 criteria (weight gain < 0.2 %). The free base oil readily absorbs moisture and CO2, forming carbamate species that compromise subsequent transformations. A monohydrochloride salt (1.0 equiv. HCl), occasionally offered as an alternative, is hygroscopic (DVS mass gain > 2 % at 80 % RH) and exhibits reduced crystallinity, leading to caking and handling difficulties during weighing. The dihydrochloride is compatible with polyethylene double‑bag packaging with desiccant. Aqueous solutions at concentrations above 50 mg/mL should be prepared fresh because slow thiazole‑ring hydrolysis at pH < 2 generates 2‑isopropyl‑4‑formylthiazole and methylamine over 48 h (LC‑MS confirmed). DMSO‑d6 stock solutions remain stable for > 12 months at 2–8 °C with < 0.5 % degradation. Full toxicological characterisation has not been completed; QSAR prediction (TEST software, US EPA) suggests an acute oral LD50 in rats (OECD 423) of > 500 mg/kg.
| Property | Free Base | Monohydrochloride | Dihydrochloride |
|---|---|---|---|
| Physical State | Pale yellow oil | Sticky solid, deliquescent | White crystalline powder |
| Decomposition / Melting (°C) | Boils > 120 (0.5 mmHg) | 95–105 (softens) | >210 (dec.) |
| Hygroscopicity (DVS at 80 % RH) | Liquefies (CO2 uptake) | >2.0 % weight gain | 0.15 % weight gain |
| Water Solubility (mg/mL) | < 5 | ≈ 50 | > 200 |
| LogD7.4 (OECD 117) | +0.8 | −0.3 | −1.2 |
| Suitability for Automated Dispensing | Poor (CV > 3 %) | Moderate (caking) | Excellent (CV ≤ 1 %) |
