Overview and Chemical Properties

Ethyl 2-amino-4-chloropyrimidine-5-carboxylate (Aladdin SKU: E692959) is a difunctionalized pyrimidine derivative featuring a nucleophilic 2-amino group, an electrophilic 4-chloro leaving group, and an ethyl ester at the 5-position. This combination of reactive handles makes it a highly valuable building block in drug discovery, enabling sequential or orthogonal transformations such as nucleophilic aromatic substitution (SNAr) at C-4 and acylation or condensation reactions involving the amine at C-2.

The compound is a crystalline solid at room temperature. It is generally soluble in common polar aprotic solvents such as DMF, DMSO, and acetonitrile, and sparingly soluble in water. The ester functionality can be hydrolyzed to the corresponding carboxylic acid under basic aqueous conditions or converted to amides via aminolysis, further expanding its synthetic utility.

Safety and Handling Guidelines

As with all fine chemical reagents, standard laboratory safety precautions should be observed when working with Ethyl 2-amino-4-chloropyrimidine-5-carboxylate. Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use.

• Personal Protective Equipment (PPE): Wear appropriate chemical-resistant gloves, a laboratory coat, and safety goggles at all times during handling.
• Ventilation: Handle the compound in a well-ventilated fume hood to minimize inhalation exposure to dust or vapors.
• Skin and Eye Contact: Avoid direct skin and eye contact. In case of contact, rinse immediately with copious amounts of water and seek medical attention if irritation persists.
• Waste Disposal: Dispose of all waste materials in accordance with local, institutional, and governmental regulations for chemical waste.

Note: Specific hazard classifications and GHS pictograms should be verified against the current SDS for E692959.

Storage Protocol

Proper storage is critical to maintaining the purity and reactivity of Ethyl 2-amino-4-chloropyrimidine-5-carboxylate over time. The following conditions are recommended:

• Temperature: Store at room temperature (15–25 °C) in a cool, dry location. Refrigerated storage (2–8 °C) may extend shelf life for long-term archiving.
• Container: Keep the compound tightly sealed in its original container to prevent moisture ingress and contamination.
• Light: Protect from prolonged exposure to direct light.
• Humidity: Store in a low-humidity environment; consider using desiccants such as silica gel when archiving for extended periods.
• Segregation: Store away from strong oxidizing agents, strong acids, and strong bases.

Review flag: Specific recommended storage temperature range should be confirmed against the product SDS and certificate of analysis (CoA) for E692959.

Synthetic Applications and Reaction Protocol

Ethyl 2-amino-4-chloropyrimidine-5-carboxylate serves as a multifunctional intermediate in the synthesis of pyrimidine-based active pharmaceutical ingredients (APIs) and research probes. Representative transformations include:

1. Nucleophilic Aromatic Substitution (SNAr) at C-4

The 4-chloro substituent is activated toward SNAr by the electron-withdrawing ring nitrogens and the 5-ester group. Amines, thiols, and alkoxides can displace the chloride under mild to moderate conditions.

• General procedure: Combine Ethyl 2-amino-4-chloropyrimidine-5-carboxylate (1.0 equiv) with the desired nucleophile (1.1–1.5 equiv) and a suitable base (e.g., Et3N, K2CO3, or DIPEA, 1.5–2.0 equiv) in a polar aprotic solvent (DMF, NMP, or MeCN) at 60–100 °C. Monitor reaction progress by TLC or LC-MS. Upon completion, work up with aqueous extraction and purify by column chromatography or recrystallization.

2. Ester Hydrolysis

The ethyl ester can be hydrolyzed to the free carboxylic acid using aqueous NaOH or LiOH (2–4 equiv) in a THF/water or EtOH/water mixture at room temperature to 60 °C, followed by acidification.

3. Condensation via the 2-Amino Group

The 2-amino group can participate in condensation reactions with carbonyl electrophiles (e.g., acid chlorides, isocyanates) to form amides or ureas, enabling construction of more complex heterocyclic architectures.

Review flag: Specific reaction yields, temperatures, and times cited above are generalizations from heterocyclic chemistry textbook knowledge and should be validated experimentally. No specific literature citations were available in the source material.

Quality Control and Purity Verification

Before use in critical synthesis steps, researchers are advised to verify the identity and purity of Ethyl 2-amino-4-chloropyrimidine-5-carboxylate (E692959) using the following standard analytical techniques:

• 1H NMR Spectroscopy: Confirm the characteristic signals for the pyrimidine ring proton (typically a singlet around δ 8.5–8.8 ppm), the NH2 protons (broad singlet), and the ethyl ester protons (quartet and triplet in the aliphatic region).
• HPLC Purity: Assess purity by reverse-phase HPLC (C18 column) using an acetonitrile/water gradient with UV detection at 254 nm. Target purity ≥95% (verify against CoA).
• LC-MS: Confirm molecular weight by electrospray ionization mass spectrometry; expected [M+H]+ at m/z 202.0 (verify against theoretical MW).
• Melting Point: Determine melting point and compare against the certificate of analysis value.

Review flag: The NMR chemical shift values and MS data cited are estimates based on structural analogy and must be confirmed against authentic reference spectra or the product CoA for E692959. Theoretical MW of C7H8ClN3O2 = 201.61 g/mol — verify.