7-Chloro-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine 1199944-04-1 98% White to Off-White Solid Triazolopyrimidine Heterocycle / Pharmaceutical & Agrochem

1. Product Overview

7-Chloro-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine (CAS 1199944-04-1) is a fused bicyclic heterocycle consisting of a [1,2,4]triazole ring fused to a pyrimidine ring, with a chloro substituent at the 7-position and a methyl group at the 5-position. With the molecular formula C₆H₅ClN₄ and a molecular weight of 168.58 g/mol, this compound is a versatile building block for constructing complex triazolopyrimidine-based APIs and agrochemicals. The electron-deficient heterocyclic core, combined with the reactive C–Cl bond, makes it ideal for nucleophilic aromatic substitution (SNAr), cross-coupling reactions, and the introduction of diverse pharmacophores.

2. Key Features and Benefits

• Fused Bicyclic Heteroaromatic Scaffold: The triazolo[1,5-a]pyrimidine system is a privileged structure in medicinal chemistry, providing a rigid, planar architecture for DNA intercalation, kinase hinge-binding, and GPCR interactions.

• Reactive C7–Cl Bond: The chloro substituent at the 7-position is activated toward SNAr by the adjacent N-atoms, enabling facile displacement with amines, alkoxides, thiols, and carbon nucleophiles under mild conditions.

• C5–CH₃ Handle: The 5-methyl group can be oxidized to –CH₂OH or –COOH, brominated (NBS) for cross-coupling, or deprotonated for C-alkylation, providing additional functionalization options.

• High Purity: Supplied at ≥95% or ≥98% (HPLC/GC), with minimal levels of dehalogenated byproduct or positional isomers.

• Stable Crystalline Form: White to off-white solid with good shelf stability under recommended storage conditions.

3. Major Applications

• Pharmaceutical Intermediate: Key building block for synthesizing triazolopyrimidine-based APIs targeting diverse therapeutic areas including oncology (kinase inhibitors), infectious diseases (antivirals, antibacterials), and CNS disorders.

• Agrochemical R&D: Used in the development of triazolopyrimidine-based herbicides (e.g., triazolopyrimidine sulfonamides like cloransulam-methyl analogs), fungicides, and insecticides.

• Nucleophilic Aromatic Substitution (SNAr) Library Synthesis: The C7–Cl undergoes clean SNAr with diverse amines (aliphatic, aromatic, heterocyclic) to generate focused libraries for high-throughput screening in drug discovery.

• Cross-Coupling Reactions: After halogen exchange (Cl→Br/I) or direct Pd-catalyzed conditions, the 5-methyl or 7-position can participate in Suzuki, Stille, and Buchwald-Hartwig couplings for scaffold diversification.

• Kinase Inhibitor Development: The triazolopyrimidine core is a known hinge-binding motif for ATP-competitive kinase inhibitors; this compound serves as a starting point for SAR exploration.

• Academic Research: Investigated in methodology development for SNAr optimization, heterocyclic functionalization, and C–H activation strategies.

4. Technical Specifications

Item Description
Product Name 7-Chloro-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine
Synonyms 5-Methyl-7-chloro-1,2,4-triazolo[1,5-a]pyrimidine; 7-Cl-5-Me-triazolo[1,5-a]pyrimidine
CAS Number 1199944-04-1
Molecular Formula C₆H₅ClN₄
Molecular Weight 168.58 g/mol
MDL Number —
Assay (Purity) ≥95% / ≥98% (HPLC / GC)
Appearance White to off-white crystalline solid or powder
Melting Point ~170–210 °C (typical for triazolopyrimidines, batch-dependent)
Boiling Point ~315.6 °C (Predicted)
Density ~1.51 g/cm³ (Predicted)
Flash Point ~144 °C (Predicted)
pKa (Predicted) ~-2.5 ± 0.5 (Pyrimidine N protonation); ~12.5 ± 0.5 (Triazole N-H)
Calculated LogP ~1.2–1.8
Polar Surface Area (PSA) ~43.1 Ų
Hydrogen Bond Donors 0
Hydrogen Bond Acceptors 4 (N ×4)
Rotatable Bonds 0 (rigid bicyclic)
Solubility Soluble: DMSO (>50 mg/mL), DMF, DCM, Chloroform, THF, Acetone, Acetonitrile, Methanol (slightly), Ethanol (slightly).
Practically Insoluble:Water (low polarity, neutral form).
Spectral Data (Predicted) ¹H NMR (CDCl₃, 400 MHz): δ 2.55 (s, 3H, C5-CH₃), 7.15 (s, 1H, C6-H), 8.50 (s, 1H, C2-H).
¹³C NMR (CDCl₃):δ 14.0 (CH₃), 110.0 (C6), 140.0 (C2), 148.0 (C7a), 152.0 (C5), 158.0 (C7), 165.0 (C3a).
SMILES Cc1cnc2nc(Cl)ncn12
InChI Key —
Storage (Powder) 2–8 °C, sealed, protected from light & moisture; stable ≥18–24 months
Sensitivity Moisture-sensitive (C–Cl can hydrolyze under forcing conditions); light-sensitive (moderate)
HS Code 2933.99.90 / 2934.99.90

5. Storage and Handling

• Storage: Store in a tightly sealed container at 2–8 °C, protected from light and moisture. For long-term storage (>12 months), keep in a desiccator. The C–Cl bond is stable under ambient conditions but may slowly hydrolyze under prolonged exposure to strong acid, base, or high temperature.

• Handling: Allow vial to reach room temperature before opening to prevent moisture condensation. Dissolve in anhydrous DMSO, DMF, DCM, or THF as required. Minimize light exposure during handling.

• SNAr Reactivity: The C7–Cl is activated toward nucleophilic aromatic substitution by the electron-withdrawing triazolopyrimidine system. Reaction with amines typically proceeds at 60–120 °C in DMSO, DMF, or NMP with or without added base (K₂CO₃, Et₃N). Alkoxides and thiolates also displace chloride efficiently.

• C5–CH₃ Functionalization: The 5-methyl group can be brominated with NBS (N-bromosuccinimide) under radical conditions for subsequent cross-coupling, or oxidized to –CH₂OH with SeO₂ or to –COOH with KMnO₄.

• Solution Stability: Prepare fresh for critical reactions. DMSO stocks are stable at -20 °C for 1–3 months. Avoid heating above 100 °C in protic solvents.

6. Safety Summary (Full SDS Highlights)

• GHS Classification: GHS07 – Warning

• Signal Word: Warning

• Hazard Statements:

• H302: Harmful if swallowed.

• H315: Causes skin irritation.

• H319: Causes serious eye irritation.

• H335: May cause respiratory irritation.

• H351: Suspected of causing cancer (structural alert—handle with caution).

• Precautionary Statements:

• P201: Obtain special instructions before use.

• P261: Avoid breathing dust/mist/vapors. Use only in a well-ventilated area or fume hood.

• P264: Wash hands, forearms, and face thoroughly after handling.

• P270: Do not eat, drink, or smoke in areas where this material is used.

• P271: Use only outdoors or in a well-ventilated area.

• P280: Wear protective gloves (nitrile), safety glasses with side shields, and lab coat.

• P301+P312: IF SWALLOWED: Call a POISON CENTER or physician if you feel unwell.

• P302+P352: IF ON SKIN: Wash with plenty of soap and water.

• P304+P340: IF INHALED: Remove person to fresh air and keep comfortable for breathing.

• P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.

• P308+P313: IF exposed: Get medical advice/attention.

• P330: Rinse mouth if swallowed.

• P337+P313: If eye irritation persists: Get medical advice/attention.

• P403+P233: Store in a well-ventilated place. Keep container tightly closed.

• P501: Dispose of contents/container in accordance with local, regional, and national regulations.

• First Aid Measures:

• Inhalation: Remove to fresh air. If breathing difficult, administer oxygen and seek medical attention.

• Skin Contact: Immediately wash with plenty of soap and water. Remove contaminated clothing. Seek medical advice if irritation or rash develops.

• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention.

• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Seek medical advice.

• Fire-Fighting Measures:

• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.

• Special Hazards: Combustion may produce highly toxic fumes including HCl (hydrogen chloride), Cl₂ (chlorine gas), CO, and NOₓ. Hydrogen chloride and chlorine are extremely toxic and corrosive.

• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.

• Spill Response:

• Avoid dust generation. Sweep up and place in a suitable closed container for disposal. Do NOT use combustible materials. Do not allow entry to drains or waterways. Ventilate area after cleanup.

• Handling & Storage:

• Handle in fume hood. Keep container closed when not in use. Store at 2–8 °C, protected from light and moisture. Keep away from strong oxidizers, strong bases, and heat sources.

• Hazardous Decomposition Products: Hydrogen chloride (HCl), chlorine gas (Cl₂), nitrogen oxides (NOₓ), carbon monoxide (CO), carbon dioxide (CO₂).

• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a potentially hazardous organohalogen compound.

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