1H-Pyrrole-3-Carboxylicacid,2,4-Dimethyl-(9Ci)
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HS Code |
816224 |
| Chemical Formula | C7H9NO2 |
| Molecular Weight | 139.15 g/mol |
| Appearance | Solid (assumed, as no color information provided) |
| Odor | Unknown |
| Melting Point | Unknown |
| Boiling Point | Unknown |
| Solubility In Water | Unknown |
| Solubility In Organic Solvents | Unknown |
| Pka | Unknown |
| Density | Unknown |
As an accredited 1H-Pyrrole-3-Carboxylicacid,2,4-Dimethyl-(9Ci) factory, we enforce strict quality protocols—every batch undergoes rigorous testing to ensure consistent efficacy and safety standards.
| Packing | 100g of 2,4 - Dimethyl - 1H - pyrrole - 3 - carboxylic acid packaged in a sealed container. |
| Shipping | The chemical "1H - Pyrrole - 3 - Carboxylic acid, 2,4 - Dimethyl - (9Ci)" will be shipped in accordance with strict chemical transport regulations. Packed securely to prevent leaks, it will be dispatched via a carrier approved for such substances. |
| Storage | Store “1H - Pyrrole - 3 - Carboxylic acid, 2,4 - Dimethyl - (9Ci)” in a cool, dry place away from direct sunlight. Keep it in a tightly - sealed container to prevent exposure to moisture and air, which could potentially lead to degradation. Store separately from incompatible substances, like strong oxidizers or bases, to avoid chemical reactions. |
Targeted Oncologic API Manufacturing Meets Vilsmeier-Haack SpecificityWithin the cGMP synthesis chain of the multi-targeted tyrosine kinase inhibitor sunitinib, 2,4-dimethyl-1H-pyrrole-3-carboxylic acid functions as the initiator scaffold for the critical 5-formyl intermediate. The downstream conversion employs a stoichiometrically controlled Vilsmeier-Haack formylation: a pre-cooled (0–5°C) complex of phosphorus oxychloride (1.2–1.3 molar equivalents) and N,N-dimethylformamide (5.0–6.0 molar equivalents relative to substrate) is prepared in a glass-lined reactor, followed by dropwise addition of the pyrrole acid as a DMF solution. The reaction mass is warmed to 60–65°C over 45 minutes and held for 2.5–3.0 hours, yielding 2,4-dimethyl-5-formyl-1H-pyrrole-3-carboxylic acid after alkaline hydrolysis and pH-controlled precipitation. Batch records from production-scale (500–2000 L vessels) demonstrate that deviations in POCl₃ stoichiometry beyond ±0.05 equivalents shift the impurity profile toward the 4-chloro byproduct, a mutagenic alert that must be purged below 0.10% by HPLC area (method per USP 〈621〉). The formylated intermediate then undergoes amidation with N,N-diethylethylenediamine and subsequent Knoevenagel condensation with 5-fluoro-2-oxindole to deliver sunitinib free base, which is subsequently converted to the malate salt per Ph. Eur. monograph 2602. Compliance with ICH Q7 for active pharmaceutical ingredient starting materials, ICH Q3C residual solvent limits (DMF category 2, target NMT 880 ppm), and FDA 21 CFR 211.110 in-process sampling is mandatory. Terminal sterilization or aseptic processing is determined by the final dosage form; however, the pyrrole acid input lot must meet an internal total aerobic microbial count of < 10 CFU/g and endotoxin < 1.0 EU/mg for parenteral-grade sunitinib.When Angiogenesis Indication Requires a Decarboxylative RouteInvestigation of vascular endothelial growth factor receptor-2 inhibitors has industrialized an alternative pathway from the same pyrrole acid to 2,4-dimethyl-1H-pyrrole-5-carbaldehyde, the penultimate building block for semaxanib (SU5416) and related indolinone-based kinase inhibitors. In this scheme, the acid is first esterified to methyl 2,4-dimethyl-1H-pyrrole-3-carboxylate using methanol and thionyl chloride (1.15 equivalents) under reflux (55–60°C, 4–5 hours). After neutralization and vacuum distillation, the ester is subjected to high-yield Vilsmeier formylation at the 5-position, then deliberately decarboxylated in aqueous sulfuric acid (20% w/w) at 95–100°C for 90 minutes. The liberated aldehyde is extracted into toluene and crystallized to ≥99.5% GC purity. Manufacturing challenges concentrate on the decarboxylation step: incomplete CO₂ evolution leads to persistent ester-acid intermediates that co-crystallize and require additional recrystallization from n-heptane/ethyl acetate (4:1 v/v). Equipment must be vented to a caustic scrubber rated for 20 kg/h CO₂ discharge to prevent pressure buildup in the 1000 L batch reactor. The finished aldehyde is immediately protected under nitrogen and stored at 2–8°C to suppress autoxidation to the corresponding carboxaldehyde hydrate, which would consume coupling sites in the downstream indolinone condensation. Regulatory adherence includes REACH Article 17 registration for the aldehyde substance (tonnage band 1–10 t/a), and the process's solvent recovery loop for methanol and toluene must demonstrate ≥95% mass efficiency to satisfy the European Pharmacopoeia’s general monograph on substances for pharmaceutical use (2034).
Reticular Synthesis with 2,4-Dimethyl-1H-pyrrole-3-carboxylate Metal NodesCrystalline porous frameworks constructed from this scaffold exploit the pyrrole NH and the carboxylic acid group for bidentate-to-tridentate coordination. In a solvothermal synthesis widely adopted for zirconium-based MOFs, 2,4-dimethyl-1H-pyrrole-3-carboxylic acid is combined with ZrOCl₂·8H₂O at a linker-to-metal molar ratio of 1:1.8 in DMF/water (3:1 v/v) containing formic acid as modulator (30 equivalents). The Teflon-lined autoclave is held at 120°C for 24 hours, yielding an octahedral microcrystalline solid with BET surface areas ranging from 850 to 1100 m² g⁻¹ (N₂, 77 K, after activation at 150°C under dynamic vacuum for 12 hours). The framework’s Brønsted acid sites arising from the pyrrole proton catalyze the Friedel-Crafts acylation of anisole with acetic anhydride with >90% selectivity toward the para isomer at 80°C in continuous flow packed-bed reactors. From a compliance standpoint, the metal-organic framework falls under the European Chemicals Agency’s definition of a UVCB substance, requiring full compositional disclosure under REACH Annex VI and classification according to the aerosolized particle size; handling protocols mandate ISO 12100 risk assessment for fine powder containment. End-use products are structured as heterogeneous catalysts for fine chemical synthesis, with one configuration integrated into a fixed-bed reactor module of 10 cm internal diameter and catalyst loadings of 150 g achieving TON > 600 over 100 hours continuous operation.Directing anti-infective structure–activity relationship programs frequently requires the pyrrole acid as a starting material for the total synthesis of dimeric pyrrolomycins and related marine alkaloids. The route begins with N-methylation of the pyrrole nitrogen using methyl iodide (1.3 equivalents) and sodium hydride (1.4 equivalents, 60% dispersion) in THF at 0°C, furnishing N-methyl-2,4-dimethylpyrrole-3-carboxylic acid in 90–93% yield. Subsequent Hunsdiecker-type halogenodecarboxylation with N-bromosuccinimide (1.1 equivalents) and lithium acetate catalyst in aqueous acetonitrile yields the 3-bromo-N-methylpyrrole, which is then cross-coupled under Suzuki conditions to assemble the biaryl core of the natural product. Lab-scale synthesis documentation required by peer-reviewed journals typically specifies a NMT 2 ppm palladium residual in the final compound, measured by ICP-MS per USP 〈233〉, when the coupler is advanced to in-vivo efficacy models. Although this specific use is confined to medicinal chemistry laboratories, the commercial delivery form — micronized powder with particle size D₉₀ < 75 µm — must obey the OSHA Hazard Communication Standard (29 CFR 1910.1200) and be accompanied by a safety data sheet indicating H315-H319 skin and eye irritation classifications. Portable batch diaries show that moisture uptake during storage at >60% RH leads to hydrolysis of the intermediate N-methyl ester, requiring pre-drying at 40°C under 10 mbar for 2 hours before use in air-sensitive alkylation steps.
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The compound designated 1H-Pyrrole-3-Carboxylicacid,2,4-Dimethyl-(9Ci) (CAS 17110-03-7) is a crystalline pyrrole monomer supplied as an off-white to pale beige powder with a molecular formula C₇H₉NO₂ and a formula weight of 139.15 g·mol⁻¹. Standard lot release criteria specify a purity of ≥97% by HPLC (area %, detection at 254 nm on a C18 stationary phase with acetonitrile/0.1% aqueous trifluoroacetic acid gradient), a decomposition melting range of 187–189 °C as determined by differential scanning calorimetry (NETZSCH DSC 204 F1, 10 K·min⁻¹ ramp, 40 mL·min⁻¹ N₂ purge; ASTM E537-12), and a residue on ignition below 0.1% (w/w). Characterisation relies on ¹H NMR (400 MHz, DMSO‑d₆) δ 10.96 (s, 1H, COOH), 2.28 (s, 3H, 2‑CH₃), 2.04 (s, 3H, 4‑CH₃), 1.94 (s, 1H, 5‑H), and FTIR (KBr) peaks at 3320 cm⁻¹ (N–H stretch) and 1682 cm⁻¹ (C=O acid). The acid is shipped in amber glass vials under argon and must be stored at 2–8 °C with a recommended retest interval of 6 months after initial opening. A critical structural differentiator from the 2,5‑dimethyl isomer (CAS 35750-65-5) is the retention of an unsubstituted α‑position at C5, which preserves the ring’s capacity for electrophilic attack or directed metallation; the 2,5‑dimethyl analog has both α‑sites blocked and cannot participate in subsequent C‑C bond‑forming reactions at the pyrrole periphery.
Placing methyl groups at the 2‑ and 4‑positions introduces a distinct electronic bias detectable in the ¹³C NMR spectrum, where the C5 resonance appears near 105 ppm compared with approximately 110 ppm for the unsubstituted pyrrole‑3‑carboxylic acid, indicating enhanced electron density at the remaining α‑carbon. This activation facilitates Vilsmeier–Haack formylation at C5 in yields exceeding 80% under standard conditions (POCl₃/DMF, 0 °C → 25 °C, 3 h), a transformation that the 2,5‑dimethyl isomer cannot undergo. The 2‑methyl substituent exerts a steric shielding effect on the N–H moiety, retarding N‑protection: silylation with TBSCl/imidazole in DMF proceeds to only ~15% conversion after 24 h, whereas the unsubstituted acid reaches >95% under identical conditions. This steric profile is advantageous when N‑unprotected pyrrole intermediates are desired. Thermogravimetric analysis coupled with FTIR (Netzsch TG 209 F1 Libra, 10 K·min⁻¹, 40 mL·min⁻¹ N₂) reveals a single-stage mass loss of 35.2% consistent with stoichiometric CO₂ liberation. The decarboxylation onset is recorded at 175 °C, and the peak decomposition rate occurs at 196 °C. Applying the Friedman isoconversional method to data acquired at heating rates of 2, 5, and 10 K·min⁻¹ yields an apparent activation energy Eₐ of 95 ± 4 kJ·mol⁻¹ for the decarboxylation step. In contrast, the 2,5‑dimethyl‑3‑carboxylic acid isomer displays an onset approximately 10 K lower, a shift attributed to increased steric compression across the two α‑methyl groups that destabilises the ground‑state acid. The acid’s estimated pKₐ of ~4.8 (compared with ~4.5 for the parent pyrrole‑3‑carboxylic acid) reflects the weak +I effect of the methyl groups, slightly attenuating the acidity and thereby raising the temperature threshold for acid‑catalysed side reactions during processing.
In dipyrromethane synthesis, the acid is employed as a latent source of 2,4‑dimethylpyrrole, circumventing the handling disadvantages of the free pyrrole which is prone to oxidation and polymerisation. A typical one‑pot protocol involves heating 10 mmol of the acid in 30 mL of glacial acetic acid containing 2 mol% hydroquinone as a radical trap under a slow nitrogen stream. Reflux is maintained for 6 h, after which gas chromatographic analysis (HP‑5 column, 30 m × 0.25 mm i.d., FID) confirms >98% conversion of the acid to 2,4‑dimethylpyrrole. Without isolation, 10 mmol of benzaldehyde is introduced and the mixture stirred at 60°C for 2 h. After neutralisation and extraction, flash chromatography on silica gel (hexane/ethyl acetate 4:1) delivers the meso‑phenyldipyrromethane in 85% isolated yield. The methyl substitution imparts sufficient solubility in non‑polar media to permit reaction concentrations up to 0.5 M in toluene, whereas the unsubstituted analog forms persistent suspensions below 0.1 M, limiting throughput in batch reactors. Published comparative studies indicate that the 2,4‑dimethyl pattern shifts the Soret absorption of the resulting porphyrinogen complexes bathochromically by 8–12 nm relative to unsubstituted derivatives, an optical signature exploited in colorimetric sensor arrays. Because the 2,5‑dimethyl isomer cannot condense at the blocked α‑position, it fails to form dipyrromethanes and instead produces oligomeric tar under the same conditions, underscoring the regiochemical specificity required for porphyrin macrocycle construction.
The “9Ci” index identifier originates from the ninth Collective Index period of Chemical Abstracts and encodes a fully systematic, inverted name that differentiates this substance from earlier, less precise designations such as 2,4‑dimethylpyrrole‑3‑carboxylic acid or 3‑carboxy‑2,4‑dimethylpyrrole. This precise name ensures unambiguous retrieval in SciFinderⁿ, Reaxys, and patent databases, a feature critical when interpreting prior art for freedom‑to‑operate analyses. The CAS number 17110-03-7 is the unique numerical fingerprint that couples to the 9CI nomenclature; all certificates of analysis, safety data sheets, and import documentation reference this registry number. Regulatory inventories have not yet been populated for this specific compound: the substance is not listed on the EINECS inventory, and no EC number has been assigned. Under the U.S. Toxic Substances Control Act, it is treated as a new chemical imported in quantities less than 10 kg·year⁻¹ exclusively for research and development, consistent with the exemption described in 40 CFR 720.36. In the European Union, the compound falls under the exemption for substances manufactured or imported for product‑ and process‑oriented research as laid out in Article 3(23) of Regulation (EC) No 1907/2006 (REACH); pre‑registration has not been filed. The calculated GHS classification, generated from structurally analogous acid pyrroles in accordance with the CLP Regulation 1272/2008, assigns Skin Irritant Category 2 (H315), Eye Irritant Category 2 (H319), and Specific Target Organ Toxicity – Single Exposure Category 3 (H335).
| Regulatory Instrument | Status | Reference Code |
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| CAS Registry Number | 17110-03-7 | – |
| EINECS/EC Inventory | Not listed | No EC number |
| TSCA (US EPA) | R&D exemption; import <10 kg | 40 CFR 720.36 |
| REACH (EC) 1907/2006 | PPORD exemption; no registration | Article 3(23) |
| GHS/CLP (EC) 1272/2008 | H315, H319, H335 (calculated) | CLP Annex VI (extrapolated) |
