5-Bromo-4,6-dimethoxypyrimidine (CAS No.: 4319-77-1) – Technical Analysis and Industrial Applications of a Highly Active Pyrimidine Intermediate

I. Basic Information and Physicochemical Properties

1. Key Chemical Parameters

• Chinese Name:
  

• English Name: 5-Bromo-4,6-dimethoxypyrimidine

• CAS No.: 4319-77-1

• Molecular Formula: $C_7{H}_{9}Br{N}_2{O}_2$

• Molecular Weight: 233.06

• Appearance: White to off-white crystalline powder, odorless, stable in air.

2. Physicochemical Properties

• Reactivity:

• Stability: Stable at room temperature; avoid prolonged contact with strong bases. High temperatures (>200℃) may cause bromine loss.

• Bromine at the 5-position exhibits strong electrophilic substitution activity, readily reacting with nucleophiles (amines, alcohols, thiols) to form diverse pyrimidine derivatives.

• Methoxy groups (-OCH?) at the 4,6-positions enhance molecular polarity and bioavailability.

• Highly soluble in methanol, ethanol, acetonitrile, DMF, etc.

• Slightly soluble in water (≈0.8g/100mL at 25℃).

• Insoluble in n-hexane.

• Melting Point: 105-107℃

• Boiling Point: 310-312℃ (atmospheric pressure)

• Density: 1.49 g/cm3

• Solubility:

• Chemical Characteristics:

II. Upstream-Downstream Industry Chain Analysis

1. Raw Materials and Synthesis Process

• React 4,6-dimethoxypyrimidine with NBS in acetic acid solvent at 80-90℃ for 6-8 hours under dark conditions.

• Purify via column chromatography or recrystallization (ethanol/water) to achieve ≥99% purity with 70-75% yield.

• Reaction Equation:
  $C_7{H}_{10}{N}_2{O}_2+NBS\stackrel{△}{\to }{C}_7{H}_{9}Br{N}_2{O}_2+succinimide$

• 4,6-Dimethoxypyrimidine (CAS: 3980-52-3)

• Brominating agents (e.g., N-bromosuccinimide [NBS], liquid bromine).

• Key Raw Materials:

• Mainstream Synthesis Route:
  Bromination Method:

2. Downstream Products and Derivatives

• Metal-organic catalysts (Pd/pyrimidine complexes) and organic optoelectronic materials (OLED hole-transport layers).

• Production of pyrimidine herbicides (e.g., Pyrazosulfuron-ethyl intermediates), fungicides, and insect growth regulators.

• Synthesis of antifungal drugs (e.g., Voriconazole intermediates), antiviral agents (HBV polymerase inhibitors), and anticancer drugs (PI3K/mTOR dual inhibitors).

• Pharmaceutical Intermediates:

• Agrochemical Intermediates:

• Materials Science:

III. Core Application Fields

1. Pharmaceutical R&D and Innovative Drugs

• Serves as a pyrimidine scaffold for PI3K/mTOR dual inhibitors (e.g., everolimus derivatives), targeting renal and breast cancers.

• Reacts with nucleoside analogs to form HBV polymerase inhibitors, blocking viral DNA replication.

• Condensation with 2,4-difluoroaniline yields Voriconazole intermediates, effective against invasive aspergillosis (clinical efficacy >85%). Bromine enhances binding to fungal cytochrome P450 enzymes.

• Antifungal Drug Intermediate:

• Antiviral Drug Precursor:

• Anticancer Drug Synthesis:

2. Agrochemical Innovation and Green Plant Protection

• Methoxy-substituted pyrimidine fungicides show >90% efficacy against wheat powdery mildew and grape downy mildew, with systemic and long-lasting protection.

• Reacts with 2,4-dichlorophenoxyacetic acid ethyl ester to produce Pyrazosulfuron-ethyl intermediates, selectively controlling weeds in rice fields (10-15g/ha dosage). Bromine enhances target selectivity.

• Herbicide Intermediate:

• Fungicide Development:

3. Materials Science and Catalysis

• Co-polymerized with carbazole derivatives for high-mobility conjugated polymers in perovskite solar cells, boosting PCE to 21% and enhancing stability.

• Forms Pd-pyrimidine complexes for Suzuki-Miyaura coupling reactions, improving catalytic efficiency by 30% over traditional ligands.

• Metal-Organic Catalyst Ligand:

• Organic Optoelectronic Materials:

IV. Technical Advantages and Market Dynamics

• Technological Barriers:

• Bromination requires controlled light-free conditions and precise NBS dosing to avoid over-bromination. Microwave-assisted synthesis reduces reaction time to 4 hours, increasing yield to 80% with <0.1% impurities.

• Production Capacity:

• Global annual capacity ≈50 tons (70% in China), mainly produced by Jiangsu Lianhua Technology and Zhejiang Yongtai Technology via NBS bromination. Emerging green bromination processes (e.g., electrochemical) are under exploration.

• Market Demand:

• Driven by antifungal drugs, novel agrochemicals, and innovative pharmaceuticals, 2024 demand grew 18% YoY. The 2025 market is projected to exceed $30 million, with 60% in pharmaceuticals and 30% in agrochemicals.

V. Safety and Storage Recommendations

• Hazards:

• Dust may irritate eyes and airways. Rat oral LD50 >2000mg/kg (low toxicity). Wear N95 masks and nitrile gloves during handling.

• Storage Conditions:

• Store in sealed, moisture-proof packaging (aluminum foil bags or lined cardboard drums) at ≤25℃, away from strong bases and light. Shelf life: 2 years.

VI. SEO Optimization Strategy

1. Keyword Placement

• Core Keywords: 5-Bromo-4,6-dimethoxypyrimidine, CAS 4319-77-1, pyrimidine intermediate, Voriconazole precursor, Pyrazosulfuron-ethyl intermediate.

• Long-Tail Keywords: 5-Bromo-4,6-dimethoxypyrimidine synthesis, antifungal drug intermediate, organic optoelectronic material intermediate.

• Multilingual Keywords: 5-Bromo-4,6-dimethoxypyrimidine, CAS 4319-77-1, pyrimidine intermediate (English-Chinese combination).