4-Pyrimidinamine, 5-methoxy- (9CI) NEW

4-Amino-5-methoxypyrimidine (CAS No.: 695-86-3) – Technical and Market Analysis of High-Value Pyrimidine Intermediates

I. Basic Information and Physicochemical Properties

1. Key Chemical Parameters

• Chinese Name: 4-Amino-5-methoxypyrimidine

• English Name: 4-Amino-5-methoxypyrimidine

• CAS No.: 695-86-3

• Molecular Formula: $C_5{H}_7{N}_{3}O$

• Molecular Weight: 125.13

• Appearance: White to off-white crystalline powder, odorless, low hygroscopicity.

2. Physicochemical Properties

• Alkalinity: Weakly basic at the 4-amino group (pKa≈5.2); forms salts with inorganic acids (e.g., hydrochloride, sulfate).

• Reactivity:

• Stability: Stable at room temperature; decomposes under strong oxidants or high temperatures (>200℃). Store in a dark, dry place.

• 5-methoxy group is stable; 4-amino group undergoes acylation, alkylation.

• Ring nitrogen atoms participate in coordination and nucleophilic substitution.

• Soluble in methanol, ethanol, DMF, etc.

• Slightly soluble in water (≈1.5g/100mL at 25℃).

• Insoluble in ether.

• Melting Point: 168-170℃

• Boiling Point: 365℃ (atmospheric pressure)

• Density: 1.29 g/cm³

• Solubility:

• Chemical Characteristics:

II. Upstream-Downstream Industry Chain Analysis

1. Upstream Raw Materials and Synthesis Process

• High-Pressure Ammonolysis Method:
  5-Methoxypyrimidine-4-one reacts with excess ammonia solution in the presence of a copper-based catalyst (e.g., CuO/Al₂O₃) at 170-190℃ and 6-8MPa for 10-14 hours.
  Purified product (≥99% purity) is obtained via acidification, neutralization, and recrystallization, with a yield of 75-80%.
  Reaction Equation:
  $C_5{H}_6{N}_2{O}_2+N{H}_3\underset{\text{High Pressure}}{\overset{\text{Catalyst}}{\to }}{C}_5{H}_7{N}_{3}O+H_{2}O$

• 5-Methoxypyrimidine-4-one (CAS: 23297-69-0)

• Ammonia solution (NH₃・H₂O) or liquid ammonia.

• Core Raw Materials:

• Mainstream Synthesis Route:

2. Downstream Products and Derivatives

• Metal-Organic Catalysts: Pd-pyrimidine complexes for Suzuki-Miyaura coupling reactions.

• Optoelectronic Materials: Hole-transport layer component in OLED devices (EQE up to 22%).

• Herbicides: Key intermediate for pyrazosulfuron-ethyl (selective control of weeds in rice fields).

• Fungicides: Precursor for pyrimidinylmethoxyacrylate fungicides (90%+ efficacy against powdery mildew).

• Antimalarial Drugs: Intermediate for Malaridine (inhibits Plasmodium DNA polymerase).

• Antiviral Drugs: Precursor for HCV drugs (e.g., sofosbuvir intermediates).

• Anticancer Drugs: Scaffold for thymidylate synthase inhibitors (e.g., 5-fluorouracil derivatives).

• Pharmaceutical Intermediates:

• Agrochemical Intermediates:

• Materials and Fine Chemicals:

III. Key Application Fields

1. Pharmaceutical R&D and Innovative Drugs

• Antimalarial Intermediates: Condensation with haloarenes yields malaridine intermediates, effective against drug-resistant malaria.

• Antiviral Precursors: Nucleoside analogs (e.g., HCV RNA polymerase inhibitors) with >95% clinical cure rates.

• Anticancer Drug Synthesis: Fluorouracil derivatives disrupt tumor cell DNA synthesis (used in gastric/colorectal cancer).

2. Agrochemical Innovation and Green Plant Protection

• Herbicide Intermediates: Reaction with 2,4-D esters produces pyrazosulfuron-ethyl intermediates (10-15g/ha dosage).

• Novel Fungicides: Pyrimidinylmethoxyacrylate derivatives with 14-day residual efficacy.

3. Materials Science and Catalysis

• Catalyst Ligands: Pd-pyrimidine complexes enhance catalytic efficiency by 30% in Suzuki-Miyaura reactions.

• Organic Optoelectronics: Copolymerized with thiophenes for high-mobility OLED hole-transport layers.

IV. Technological Advantages and Market Dynamics

• Technical Barriers:

• High-pressure ammonolysis requires precise catalyst control. Microchannel flow technology reduces reaction time to 5 hours, lowers impurities to <0.1%, and increases yields to 85%.

• Production Capacity:

• Global capacity ≈100 tons/year; China accounts for 70% (major producers: Zhejiang Yongtai Technology, Jiangsu Zhongqi Technology).

• Market Demand:

• Driven by antimalarial, HCV, and agrochemical demand, 2024 demand grew 20% YoY. 2025 market projected to exceed $40 million, with pharmaceuticals dominating 70%.

V. Safety and Storage Recommendations

• Hazards:

• Dust irritates eyes/respiratory tract; LD50 >2000mg/kg (oral, rat). Wear dust masks/gloves.

• Storage:

• Seal in cool, dry conditions (≤25℃); use moisture-barrier packaging (e.g., foil bags). Avoid oxidizers/acids.

VI. SEO Optimization Strategy

1. Keyword Layout

• Core Keywords: 4-Amino-5-methoxypyrimidine, 695-86-3, pyrimidine intermediates, antimalarial API, pyrazosulfuron intermediate.

• Long-Tail Keywords: 4-Amino-5-methoxypyrimidine synthesis, HCV drug intermediates, metal-organic catalyst ligands.