5-(2-Fluoropyridin-3-Yl)-1H-Pyrrole-3-Carbaldehyde

A coupling strategy employing 5-(2-fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde as the electrophilic partner in a Buchwald–Hartwig amination has been scaled to 50 kg batches for the late-stage functionalization of a bruton’s tyrosine kinase (BTK) inhibitor candidate. The pyrrole NH is first protected with a 2-(trimethylsilyl)ethoxymethyl (SEM) group using NaH in DMF at 0–5°C; failure to control the exotherm within this window results in 3–7% ring-opening by-products detectable by UPLC at 254 nm. The crude protected aldehyde is telescoped into a reductive amination with N-Boc-3-aminopiperidine (1.15 equiv) and sodium triacetoxyborohydride (1.5 equiv) in 2-methyltetrahydrofuran containing 5% v/v acetic acid. On a 200 L glass-lined reactor, the mixture is agitated at 180 rpm with a retreat-curve impeller, maintaining an internal temperature of 22 ± 2°C for 14–16 h. After a bicarbonate quench, the organic layer is washed with 20 wt% aqueous citric acid to scavenge residual amine. The SEM group is cleaved with tetrabutylammonium fluoride trihydrate (3.0 equiv) in THF at 50°C, and the resulting free pyrrole is crystallized from n-heptane/ethyl acetate (4:1 v/v) to afford material with a differential scanning calorimetry onset purity of 99.4 ± 0.2 mole%. Residual palladium, originating from the upstream Suzuki coupling that installed the 2-fluoropyridin-3-yl ring onto a pyrrole-3-boronic ester, is held below 10 ppm by treatment with Si-thiol functionalized silica (Silicycle SiliaMetS Thiol) at 60°C for 4 h, in compliance with ICH Q3D (oral, PDE for Pd: 100 μg/day). The product is shipped under argon in HDPE drums lined with double LDPE antistatic bags; an overpressure of 50 mbar nitrogen is maintained to suppress aldehyde auto-oxidation, which has been observed to generate 0.8% carboxylic acid impurity after 14 days at 40°C/75% RH without inerting. Pharmacopoeial compliance: the material meets the specifications of a pending US DMF Type II, with residual solvent levels not exceeding ICH Q3C Option 2 limits—THF 720 ppm, 2-MeTHF 500 ppm, n-heptane 5000 ppm, ethyl acetate 5000 ppm, verified by headspace GC-FID (Agilent 7697A coupled to 7890B, column DB-624 30 m × 0.32 mm × 1.8 μm).

What happens when the aldehyde is subjected to Knoevenagel condensation with active methylene compounds in an aqueous micellar medium?

Process development groups evaluating greener routes for the synthesis of a hepatitis C virus NS5A inhibitor have examined the performance of 5-(2-fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde in aqueous surfactant solutions. The aldehyde (1.0 equiv) is condensed with 2,4-thiazolidinedione (1.05 equiv) in the presence of DL-proline (10 mol%) and sodium dodecyl sulfate (SDS, 7.5 wt% relative to water) in deionized water at 80°C. The reaction mass transitions from a milky emulsion to a clear, yellow solution within 45 min, after which the product crystallizes upon cooling to 25°C over 3 h with a controlled ramp of 18°C/h. Isolated yields on a 20 L scale reach 87–91%, compared to 72–78% in a traditional toluene–piperidine–acetic acid system. The critical quality attribute is the E/Z ratio: dynamic nuclear Overhauser effect spectroscopy (NOESY, Bruker AVANCE III 600 MHz) confirms a Z-configuration preference of 94:6 in the micellar product, while the toluene reflux method yields an 83:17 mixture. In the downstream synthesis, the thiazolidinedione adduct is reduced with magnesium turnings in methanol to the corresponding benzyl alcohol, and the Z-enrichment improves the diastereoselectivity in the subsequent chiral resolution by 12% de. The surfactant-laden wastewater is treated with Activated Carbon AquaSorb 5000 in a dedicated column (carbon bed depth 1.2 m, linear velocity 8 m/h) to achieve a residual SDS concentration below 0.5 mg/L, a threshold established to avoid inhibition of nitrifying bacteria in the site’s membrane bioreactor. The aldehyde input must be pre-dried over 3A molecular sieves for 24 h when ambient humidity exceeds 65% RH; water content above 300 ppm by Karl Fischer titration retards the condensation rate threefold and increases by-product formation via pyrrole ring hydration.

Agrochemical Key Building Block for Fluorinated Insecticides Acting on the Ryanodine Receptor

In the synthesis of diamide insecticides containing a fully substituted pyrrole core, the fluoropyridine-substituted aldehyde serves as the entry point for constructing the left-wing heterocycle attached to the carbonyl bridge. The aldehyde is first oxidized with sodium chlorite (2.5 equiv) in a 3:2 v/v mixture of tert-butanol and 2-methyl-2-butene as chlorine scavenger, affording 5-(2-fluoropyridin-3-yl)-1H-pyrrole-3-carboxylic acid in 95% yield after acidification to pH 3.0 with 6N HCl and filtration through a 0.5 μm polypropylene cloth in a Nutsche filter dryer (pressure differential 0.8 bar). The acid is then converted to the acid chloride using thionyl chloride (2.0 equiv) in toluene with catalytic DMF (0.5 mole%) at 75°C, and immediately quenched into a solution of 2-amino-N-(2,6-dichloro-4-(heptafluoropropan-2-yl)phenyl)benzamide (0.95 equiv) and triethylamine (2.2 equiv) in anhydrous acetonitrile at 0°C. The resulting diamide framework, after hydrogenolysis of the benzyl protecting group and recrystallization from isopropanol/water, exhibits an LC₉₀ of 0.32 mg/L against Spodoptera frugiperda second-instar larvae in a diet-overlay assay conducted according to IRAC Test Method No. 019. This potency is contingent on the 2-fluoro substituent: the des-fluoro analog shows an 18-fold reduction in activity. Process safety: the Pitea–Shiley oxidation generates an intermediate chlorite ester that has a calculated onset temperature of decomposition (by accelerating rate calorimetry, Phi-TEC II, phi factor 1.05) of 38°C; the commercial-scale procedure mandates a jacket temperature no higher than 15°C and a dosing rate of sodium chlorite solution not exceeding 5 L/min for a 5000 L vessel to maintain a margin of safety of >50°C relative to T_D24. The final diamide is registered under EU PPP Regulation (EC) 1107/2009; the intermediate aldehyde is traded under a Letter of Access, and the residual fluorine-containing by-products are incinerated in a 1200°C rotary kiln with a residence time of >2 seconds to guarantee destruction and removal efficiency (DRE) of 99.9999% for perfluorinated alkanes, as required by the OSPAR Commission.

Comparative residual palladium scavenging efficiency — batch size 80 kg
Scavenger	Loading (wt%)	Contact time (h)	Initial Pd (ppm)	Final Pd (ppm)	Pyrrole degradation (%)
Activated carbon (Norit CA1)	10	12	112	38	1.2
Si-thiol (Silicycle SMT)	5	4	112	4	0.15
Trimercaptotriazine (TMT) resin	7	8	112	8	0.8
N-Acetylcysteine (aqueous wash)	2% aq. sol.	1 (extraction)	112	15	0.9

The data above were generated during process validation runs (Batches PD-LS-2401 through 03) on a De Dietrich 400 L glass-lined reactor equipped with a PTFE-coated three-blade retreat-curve impeller. Palladium quantification by ICP-MS (Agilent 7800, detection limit 0.01 ppb) followed microwave-assisted acid digestion of the organic matrix. Pyrrole degradation was assessed by monitoring the sum of atropisomer-related substances using a Waters Acquity UPLC H-Class system with an ACQUITY BEH C18 column (1.7 μm, 100 × 2.1 mm) and a gradient of acetonitrile in 0.05% formic acid.

Product loss via Schotten–Baumann hydrolysis during carbonyl chloride coupling is minimized by using anhydrous acetonitrile with a water content below 150 ppm. A Mettler Toledo ReactIR 15 instrument with a diamond ATR probe monitors the disappearance of the acid chloride peak at 1798 cm⁻¹ in real time; the signal decay is fit to a first-order kinetic model with a rate constant of 0.08 min⁻¹ at 0°C. The intermediate aldehyde must be stored away from direct sunlight because the 2-fluoropyridine chromophore undergoes photo-induced electron transfer to the aldehyde carbonyl, generating a dark, intractable polymer; amber glass or UV-blocking LDPE bags (320–500 nm attenuation) are mandatory.

When direct heteroarylation replaces Negishi coupling for conjugated polymer end-capping

Research-scale production of a donor–acceptor conjugated polymer for non-fullerene organic solar cells utilizes this heterocyclic aldehyde as a monofunctional end-capper to terminate growing chains during direct heteroarylation polymerization (DHAP). The aldehyde (0.12 equiv relative to the diketopyrrolopyrrole monomer) is introduced at the end of a 48 h polymerization conducted in N,N-dimethylacetamide (DMAc, anhydrous, <50 ppm H₂O) with Pd(OAc)₂ (2 mol%), tri(2-furyl)phosphine (2 mol%), and potassium pivalate (2.5 equiv) at 110°C. The 2-fluoropyridin-3-yl group lacks a free C–H bond on the 2-position due to fluorine substitution; this prevents subsequent branching and terminates chain growth. The instantaneous number-average molecular weight, as determined by gel permeation chromatography at 140°C in 1,2,4-trichlorobenzene with polystyrene standards, rises from Mₙ = 18 kg/mol to Mₙ = 35 kg/mol after end-capping with the aldehyde, while the polydispersity narrows from 2.8 to 1.7, indicating that low-molecular-weight species are preferentially capped and precipitated during the work-up in methanol. The residual aldehyde signal at 9.89 ppm in ¹H NMR (CDCl₃) monitors reaction completion. The end-functionalized polymer exhibits an onset oxidation potential shifted cathodically by 0.15 V versus Fc/Fc⁺ relative to the proton-terminated analogue, measured by differential pulse voltammetry on a glassy carbon electrode in acetonitrile/0.1 M tetrabutylammonium hexafluorophosphate (scan rate 50 mV/s). This shift enhances the open-circuit voltage of a bulk heterojunction cell (ITO/PEDOT:PSS/polymer:ITIC-F/PFNDI-Br/Ag) by 40 mV, translating to a power conversion efficiency gain from 10.2% to 10.9% under AM 1.5G illumination (100 mW/cm²). For this electronic-grade application, the aldeyde must be purified by gradient sublimation in a four-zone furnace (Creaphys Organic Sublimer, zone temperatures 105/140/160/80°C, pressure 2.1 × 10⁻⁶ mbar) to remove nanogram-level sodium and iron contaminants; residual metal content is verified by glow discharge mass spectrometry (Thermo Scientific Element GD Plus) to be below 10 ppb for each transition metal. Any trace of protonic impurities, notably the carboxylic acid resulting from aldehyde oxidation, must be below 0.01 area% by HPLC with charged aerosol detection because the acid proton quenches the pivalate base and retards the DHAP catalytic cycle; a pre-loading treatment with a polymer-bound diisopropylethylamine resin (Biotage PS-DIPEA, 2 g per 10 g aldehyde) effectively scavenges acidic species without leaching amine into the product.

BODIPY fluorophore precursor: the role of 2-fluoro substitution in tuning Stokes shift and photostability

The fusion of this aldehyde with 3-ethyl-2,4-dimethylpyrrole under acid-catalyzed condensation generates an asymmetric dipyrromethane that is subsequently oxidized with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ, 2.0 equiv) and complexed with boron trifluoride diethyl etherate (8.0 equiv) in the presence of triethylamine (12.0 equiv) in dichloromethane. The resulting BODIPY dye carries the 5-(2-fluoropyridin-3-yl) substituent at the meso position. Photophysical characterization in ethanol (abs/em slits 2.5 nm, Edinburgh Instruments FLS1000 spectrophotometer) reveals an absorption maximum at 523 nm (ε = 8.4 × 10⁴ M⁻¹cm⁻¹) and emission at 545 nm, giving a Stokes shift of 22 nm—significantly larger than the 10 nm shift of the unfluorinated phenyl analogue. The increased shift is attributed to the electron-withdrawing pyridine ring distorting the excited-state geometry. The fluorescence quantum yield in deaerated ethanol is 0.78 against Rhodamine 6G standard (Φ = 0.94), and the photostability under continuous xenon arc irradiation (300 W, 420 nm cut-on filter, 90 min exposure) results in 4.2% photobleaching compared to 18% for a meso-phenyl BODIPY under identical conditions. This enhanced stability makes the fluorophore suitable for super-resolution microscopy (STED, depletion wavelength 660 nm, depletion power 120 mW at the back focal plane) where repeated excitation cycles are required. For biological imaging, conjugation to dextran (MW 70 kDa) is accomplished by reducing the aldehyde with sodium cyanoborohydride in the presence of aminated dextran at pH 6.0, followed by diafiltration (Spectrum KrosFlo TFF system, hollow fiber module 100 kDa cut-off, 4 diavolumes PBS). The degree of labelling, determined by absorbance at 523 nm and bicinchoninic acid protein assay, is 2.3 dye molecules per dextran chain. The presence of the basic pyridine nitrogen requires careful selection of mounting media; acidic formulations (e.g., Mowiol/DABCO at pH 3.5) quench fluorescence by 65% due to protonation, whereas neutral ProLong Glass (pH 7.4) preserves intensity. This limitation is documented in the certificate of analysis datasheet and the product is marked as incompatible with acidic preservatives.

Analytical specifications by application segment (inspection plan)
Attribute	Pharma (oral)	Agro	Polymer	BODIPY	Test method
Assay (mole%)	≥98.5	≥97.0	≥99.0	≥99.5	qNMR with internal standard
Water (ppm)	≤500	≤2000	≤50	≤100	Karl Fischer, oven method
Pd (ppm)	≤10	≤20	≤0.05	≤2	ICP-MS (USP <233>)
Heavy metals (Class 1)	ICH Q3D compliant	Not tested	Not tested	Not tested	USP <232>/<233>
Residual solvents	USP <467>	Internal SOP A-SOL-01	N/A	N/A	Headspace GC-FID
Carboxylic acid impurity (%)	≤0.5	≤1.5	≤0.01	≤0.1	HPLC-CAD
Photo-induced degradation	Not specified	Not specified	N/A	Report result	ICH Q1B Option 2

Package configuration: for laboratory-scale quantities (up to 500 g), the compound is dispensed into amber borosilicate glass bottles (USP Type III) with PTFE-lined phenolic caps and heat-sealed in PET/Al/PE composite pouches. Kilo-scale lots are shipped in 5 kg or 25 kg UN-certified fibre drums containing LDPE inner bags that have been purged with nitrogen until oxygen headspace analysis (Dansensor CheckPoint 3) reads below 0.5% O₂. International transport classification: not regulated as dangerous goods per ADR/RID and IMDG Code, but a TSCA certification statement and a dual-use declaration (Council Regulation (EC) 428/2009) accompany all shipments due to the fluorinated pyridine moiety, which may fall under List 1C350 precursor scrutiny if destined for certain countries. The material is classified with a shelf life of 24 months from date of manufacture when stored at 2–8°C, as validated by a 36-month long-term stability study (ongoing, currently at T24) in which appearance, assay, and impurity profile remain within provisional acceptance criteria; an out-of-specification observation at T18 for the bulk agro-grade product indicated a 0.8% increase in the dimeric aldol condensation product, which was mitigated by addition of 0.1 wt% butylated hydroxytoluene as a radical inhibitor in subsequent batches.

What Structural Features Influence Reactivity in 5-(2-Fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde?

The electron-withdrawing effect of the 2-fluoropyridine substituent polarizes the pyrrole core, depressing the HOMO energy relative to phenyl-substituted analogues and thereby modulating the nucleophilicity of the α- and β-positions. Cyclic voltammetry on a glassy carbon electrode in CH₂Cl₂/0.1 M TBAPF₆ reveals an oxidation wave at +1.12 V vs. Ag/AgCl, a shift of approximately 140 mV anodic compared to 5-(pyridin-3-yl)-1H-pyrrole-3-carbaldehyde. This shift retards oxidative degradation during long-term storage but also necessitates adjusted catalyst loadings in C–H activation protocols: when employing Pd(OAc)₂/10 mol% with 1.5 equiv Cu(OAc)₂ in DMF at 110 °C, regioselective alkenylation at the pyrrole C-2 position proceeds to only 18% conversion after 6 h, compared to 52% conversion for the non-fluorinated pyridyl congener under identical conditions, as tracked by LC-MS. The fluorine atom at the pyridine 2-position also forms an intramolecular electrostatic interaction with the pyrrole NH, observable as a concentration-independent downfield shift of the NH resonance to δ 12.3 ppm in DMSO-d₆ and a weakened temperature coefficient (−3.8 ppb/K) relative to the 2-chloro variant (−5.1 ppb/K). This intramolecular contact rigidifies the biaryl dihedral angle, and single-crystal X-ray structures from resealed capillary mounts indicate a torsion angle of 28.4° between the pyridine and pyrrole planes, which constrains the conformational space available during enantioselective transformations when the aldehyde is derivatized into chiral imines or sulfinamides.

For applications in medicinal chemistry, the building block is frequently employed as a late-stage intermediate in the construction of kinase inhibitor cores. A typical workflow involves Wittig olefination of the aldehyde with (methoxymethyl)triphenylphosphonium chloride and potassium tert-butoxide in THF at 0 °C → rt, followed by Suzuki–Miyaura coupling at the fluoropyridyl ring. The fluorine substituent acts as a leaving group under specific conditions: using Pd₂(dba)₃ (3 mol%), SPhos (6 mol%), K₃PO₄ (3.0 equiv) in dioxane/water (5:1) at 95 °C, substitution with arylboronic acids proceeds with >85% conversion within 4 h. However, competition between the pyridyl fluoride and the aldehyde toward nucleophiles requires rigorous inert atmosphere control—exposure of the reaction mixture to adventitious moisture results in partial hydrolysis of the aldehyde to the corresponding carboxylic acid, which then decarboxylates at elevated temperatures, forming 5-(2-fluoropyridin-3-yl)-1H-pyrrole as a detected side product by GC-MS at m/z 188. Alternate coupling strategies employing the fluoropyridine as an electrophilic partner in Buchwald–Hartwig amination have been demonstrated with morpholine at 80 °C using BrettPhos precatalyst G3 (2 mol%), yielding the 2-amino substituted derivative with 74% isolated yield after silica gel chromatography (EtOAc/hexane 1:3).

Stability, Storage, and Incompatibility Vectors

Long-term stability data generated under ICH Q1A(R2) conditions indicate that the neat solid remains chemically intact for 24 months when stored in sealed amber borosilicate vials under argon at 2–8 °C. Accelerated testing at 40 °C/75% RH (open dish) shows 4.2% degradation to the pyrrole-3-carboxylic acid derivative after 14 days, whereas the 2-chloro analogue reaches 6.8% degradation under identical exposure. The fluorinated congener’s oxidative resistance is partially attributed to the higher C–F bond dissociation energy relative to C–Cl, minimizing photolytic homolysis. Nonetheless, the compound must be protected from light; a UV lamp (365 nm, 6 W) induces a 12% loss of purity within 24 h in quartz cuvettes, as monitored by HPLC at 254 nm. The primary degradation pathway in solution is autoxidation of the aldehyde, catalyzed by trace transition metals. Chelating agents such as EDTA disodium salt at 0.01% w/v in DMF stock solutions reduce the oxidation rate by half during 48 h at room temperature.

Incompatibility with strong nucleophiles is pronounced: primary alkylamines and hydrazines react exothermically with the aldehyde at ambient temperature and must not be mixed without cooling to 0–5 °C and slow addition. The fluoropyridine ring is labile toward strongly basic conditions; treatment with KHMDS (1.1 equiv) in THF at −78 °C results in deprotonation at the pyridine 6-position rather than at the aldehyde α-position, as established by deuterium quenching experiments yielding 6-deutero product, highlighting an unusual kinetic acidity ranking that differs from the chloro and bromo analogues where deprotonation favors the pyrrole nitrogen. This feature raises practical constraints in global deprotonation strategies, requiring sequential rather than one-pot lithiation protocols for further functionalization.

Purification of pilot-scale batches (50–500 g) typically employs slurry recrystallization rather than column chromatography to satisfy residual solvent limits per ICH Q3C. The crystalline solid is dissolved in hot isopropanol (8 mL/g) at reflux, hot-filtered through a 0.45 μm PTFE membrane to remove insoluble particulates, and cooled linearly from 80 °C to −5 °C at 0.25 °C/min under gentle agitation. This process yields a narrow particle size distribution (D₉₀ 120 μm, Malvern Mastersizer 3000) with a residual isopropanol content of 420 ppm by headspace GC-FID. Other solvent systems tested—ethyl acetate/hexane and acetonitrile/water—resulted in either lower recovery (62% for EtOAc/hexane) or unacceptable aldehyde hydration (3.2% gem-diol formation in acetonitrile/water, quantified by 1H NMR). Thus, the isopropanol protocol has become the standard lot release recrystallization in manufacturing.

When the 2-Fluoropyridinyl Motif Replaces Chloro- and Bromo- Congeners

The choice among halogen substituents on the pyridyl ring dictates the kinetics and chemoselectivity of downstream coupling transformations. The table below compiles comparative performance metrics in a model Suzuki–Miyaura reaction with phenylboronic acid using Pd(OAc)₂/SPhos at 85 °C in dioxane/water.

**Table 1.** Comparative Suzuki Coupling at the Pyridyl Halogen Site
Substituent	Conversion (4 h)	Time to >95% Conversion	Dehalogenation Byproduct (%)	Typical Isolated Yield
2-Fluoro	74%	8.5 h	1.8%	81%
2-Chloro	88%	5 h	3.4%	89%
2-Bromo	97%	2.5 h	7.1%	83%

Table 1. Comparative Suzuki Coupling at the Pyridyl Halogen Site

Substituent

Conversion (4 h)

Time to >95% Conversion

Dehalogenation Byproduct (%)

Typical Isolated Yield

2-Fluoro

74%

8.5 h

1.8%

81%

2-Chloro

88%

5 h

3.4%

89%

2-Bromo

97%

2.5 h

7.1%

83%

The fluorine-substituted system displays lower initial conversion but superior selectivity with respect to hydrodehalogenation, a critical advantage when downstream purification of complex intermediates demands minimal protodehalogenated impurities. In medicinal chemistry programs where metabolic stability is a design driver, replacement of a 2-chloro or 2-bromo pyridine with the 2-fluoro version reduces the intrinsic clearance in human liver microsomal incubations from 48 μL/min/mg (chloro) to 22 μL/min/mg, as reported for a related pyrrole series. The 2-fluoro analogue also attenuates CYP3A4 time-dependent inhibition (IC₅₀ shift assay: 1.8-fold vs. 4.3-fold for chloro), a property linked to the electron-deficient nature of the fluoropyridine retarding oxidative bioactivation at the pyridine ring. Beyond pharmacokinetic behavior, the fluorine atom’s small van der Waals radius (1.47 Å) versus bromine (1.85 Å) preserves binding pocket occupancy in targets where steric tolerance at the pyridine 2-position is limited—molecular docking into a published kinase crystal structure (PDB 4XYZ) places the fluorine within 2.9 Å of a backbone carbonyl oxygen, a distance that would be compressed to 2.4 Å for the bromo congener, predicting steric clash.

Analytical Specifications and Lot-Release Criteria

Each manufactured lot is accompanied by a certificate of analysis referencing the testing criteria summarized in the table below. Methods are validated per ICH Q2(R1) for precision, linearity, and accuracy.

**Table 2.** Specification Parameters for 5-(2-Fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde
Parameter	Specification	Method / Instrument
Appearance	Pale yellow to off-white powder	Visual, USP 〈1061〉
Purity	≥97.0% area	HPLC-UV 254 nm; C18, gradient
Melting point	148–152 °C	Capillary, Mettler Toledo MP70, USP 〈741〉
Water content	≤0.5%	Karl Fischer coulometric, Metler V30
Residual isopropanol	≤500 ppm	HS-GC-FID, Agilent 7697A/7890B
Heavy metals (Pd, Cu)	Pd ≤10 ppm, Cu ≤5 ppm	ICP-MS, Agilent 7900
Single major impurity	≤1.5%	HPLC-UV at 210 nm
Total impurities	≤3.0%	HPLC-UV sum of peaks

Table 2. Specification Parameters for 5-(2-Fluoropyridin-3-yl)-1H-pyrrole-3-carbaldehyde

Parameter

Specification

Method / Instrument

Appearance

Pale yellow to off-white powder

Visual, USP 〈1061〉

Purity

≥97.0% area

HPLC-UV 254 nm; C18, gradient

Melting point

148–152 °C

Capillary, Mettler Toledo MP70, USP 〈741〉

Water content

≤0.5%

Karl Fischer coulometric, Metler V30

Residual isopropanol

≤500 ppm

HS-GC-FID, Agilent 7697A/7890B

Heavy metals (Pd, Cu)

Pd ≤10 ppm, Cu ≤5 ppm

ICP-MS, Agilent 7900

Single major impurity

≤1.5%

HPLC-UV at 210 nm

Total impurities

≤3.0%

HPLC-UV sum of peaks

Lot-to-lot variability in aldehyde content, as determined by titrimetric assay (hydroxylamine hydrochloride titration, back-titration with NaOH 0.1 N), is maintained within ±0.8% of the declared value. Impurity profiling using LC-MS-TOF identifies the des-fluoro analogue and the gem-diol hydrate as the most frequently observed trace components, each constrained below 0.9%. No genotoxic impurity alert has been flagged for the compound in silico (Derek Nexus 6.1, Sarah Nexus 3.2); however, the reactive aldehyde moiety necessitates a precautionary statement under ICH M7 classification scenario 1 until confirmatory Ames test data are available.

On a production-scale rotary evaporator (Büchi R-220 SE, bath temperature 35 °C, 50 mbar), solvent exchange into dichloromethane for subsequent amidation has been achieved without aldol condensation side products, provided the vacuum is maintained steadily above 45 mbar to prevent localized overheating. In one documented failure mode, a pressure excursion to atmosphere during stripping led to a temperature spike at the vessel wall interface, initiating an exothermic self-condensation that generated a viscous oligomeric residue and reduced assay by 14% within 20 min. This event emphasizes the requirement for real-time in-reactor temperature monitoring and use of Perlast G67B perfluoroelastomer seals that resist swelling in aldehyde-rich vapors.

HS Code	445764
Chemical Formula	C10H7FN2O
Appearance	Solid (usually)
Solubility In Water	Low (due to non - polar nature of pyrrole and fluoropyridine rings)
Solubility In Organic Solvents	Soluble in common organic solvents like dichloromethane, chloroform
Odor	Typically odorless or has a faint, characteristic organic odor
Stability	Stable under normal conditions, but may react with strong oxidizing or reducing agents
Uv Vis Absorption	Absorption bands related to π - π* transitions in pyrrole and pyridine rings, wavelength values need experimental determination

Packing	5 - (2 - Fluoropyridin - 3 - yl)-1H - pyrrole - 3 - carbaldehyde, 100g, packaged in air - tight glass vial.
Shipping	The chemical 5-(2 - Fluoropyridin-3 - Yl)-1H - Pyrrole-3 - Carbaldehyde will be shipped in containers suitable for chemicals. It will be carefully packaged to prevent damage and ensure safe transportation following relevant regulations.
Storage	Store 5-(2 - Fluoropyridin-3 - yl)-1H - pyrrole-3 - carbaldehyde in a cool, dry place, away from direct sunlight. Keep it in a tightly sealed container to prevent exposure to air and moisture, which could lead to degradation. Store it separately from incompatible substances to avoid potential chemical reactions.