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5‑(4‑Bromophenyl)‑4,6‑dichloropyrimidine (CAS: 146533‑41‑7) is a tri‑halogenated pyrimidine derivative with the molecular formula C₁₀H₅BrCl₂N₂ and a molecular weight of 303.97 g/mol. It appears as a white to light‑yellow crystalline powder (melting point 97–102 °C) and is slightly soluble in chloroform and DMSO. The structure consists of a central pyrimidine ring bearing two chlorine atoms at the 4‑ and 6‑positions and a 4‑bromophenyl substituent at the 5‑position. This specific tri‑halogenated substitution pattern creates a uniquely reactive architecture that is difficult to replicate with other substitution patterns: the two chlorine atoms serve as orthogonal leaving groups for sequential nucleophilic aromatic substitution (SNAr), while the bromine atom on the pendant phenyl ring provides an additional handle for cross‑coupling chemistry (Suzuki‑Mori, Buchwald‑Hartwig, Sonogashira) after the pyrimidine core has been modified.

As the unequivocal key starting material for the FDA‑approved dual endothelin receptor antagonist Macitentan (Opsumit®), the compound occupies a critical position at the front end of the pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF) drug supply chain, and is the preferred tri‑halogenated pyrimidine building block in pharmaceutical, agrochemical and advanced material industries worldwide.

Core Application Fields

Market demand for 5-(4-bromophenyl)-4,6-dichloropyrimidine is highly concentrated in four high‑value sectors: Macitentan API manufacturing (≈45‑50% of total consumption), agrochemical intermediate synthesis (≈20‑25%), anticancer & antiviral drug discovery (≈10‑15%), and advanced materials & OLED fabrication (≈5‑10%). The compound‘s strategic role as the key starting material for Macitentan accounts for the majority of growth, while expanding applications in crop protection, kinase inhibitors and organic electronics are rapidly diversifying its demand base.

1. Macitentan API Manufacturing – The Dominant Demand Driver (≈45‑50% of total consumption). 5‑(4‑Bromophenyl)‑4,6‑dichloropyrimidine is the unequivocal key starting material for Macitentan (Opsumit®), an orally active, non‑peptide dual endothelin receptor antagonist (ERA) approved by the FDA for the treatment of pulmonary arterial hypertension (PAH) and subsequently for idiopathic pulmonary fibrosis (IPF). In the industrial manufacturing route, Macitentan is assembled via lithium amide‑mediated nucleophilic substitution starting directly from this tri‑halogenated pyrimidine building block, achieving an overall yield of approximately 62% in a telescoped process. The compound has been specifically designated as a KSM‑I (Key Starting Material‑I) impurity reference standard, enabling its use in analytical method development (AMD), analytical method validation (AMV) and quality control (QC) for Abbreviated New Drug Applications (ANDAs) and commercial Macitentan production.

Macitentan achieved net sales of USD 1.93 billion in 2025, as reported by Johnson & Johnson. The global PAH drug market was valued at USD 7.1 billion in 2025 and is projected to grow at a CAGR of 5.0‑5.5% through 2033, driven by the continued adoption of combination therapies including Macitentan, increased diagnosis rates for PAH and the expansion of IPF treatment indications. The global endothelin receptor antagonist market is expected to expand at a CAGR of 6.3% during the same period, positioning 5‑(4‑bromophenyl)‑4,6‑dichloropyrimidine to directly capture a substantial share of this growth.

2. Agrochemical Intermediate Synthesis (≈20‑25% of total consumption). The tri‑halogenated pyrimidine scaffold exhibits robust stability and predictable reactivity under standard conditions, making it highly valuable for agrochemical development. The compound is employed in the formulation of agrochemicals, where it acts as a key building block for herbicides and fungicides, enhancing crop protection and improving agricultural yield. It is primarily used as a building block or intermediate in the synthesis of agrochemicals and other fine chemicals. Due to its unique structure and reactivity, it offers versatility in creating compounds with diverse biological activities. Patents disclose triazole derivatives prepared from this scaffold that exhibit antifungal activity in both human and agricultural applications, further expanding its utility in the crop protection sector. As global demand for heterocyclic crop protection agents increases – with the global herbicide and fungicide market projected to reach USD 120‑130 billion by 2030 – this segment is expected to grow at a CAGR of 5‑7%.

3. Anticancer & Antiviral Drug Discovery (≈10‑15% of total consumption). The compound is a key intermediate in the development of various pharmaceuticals, particularly in the synthesis of antiviral and anticancer agents. In synthetic chemistry, 5‑(4‑bromophenyl)‑4,6‑dichloropyrimidine can undergo sequential SNAr reactions (exploiting the C‑4 and C‑6 chlorine atoms) followed by cross‑coupling chemistry at the C‑5 bromophenyl ring, enabling medicinal chemists to rapidly generate libraries of diversely substituted pyrimidine derivatives for SAR exploration. This orthogonal functionalisation strategy has been exploited to prepare C‑5 arylated pyrimidine analogues via Suzuki–Miyaura cross‑coupling reactions using a Pd(0) catalyst. The compound’s robust structure and predictable reactivity make it a platform molecule for fragment‑based drug discovery (FBDD) targeting kinases, GPCRs and other therapeutically relevant protein families. It is also used to synthesise N‑(5‑(4‑bromophenyl)‑6‑chloropyrimidin‑4‑yl)butane‑1‑sulfonamide and other bio‑active compounds, and is extensively utilized in the synthesis of bioactive compounds aiding the development of pharmaceuticals with potential therapeutic benefits.

4. Advanced Materials & Organic Electronics (≈5‑10% of total consumption). The rigid, electron‑deficient pyrimidine core, combined with the heavy halogen atoms (Br, Cl), provides desirable electronic properties for advanced material applications. Pyrimidine derivatives built on this scaffold are actively being explored as components of OLED (organic light‑emitting diode) materials, including electron‑transport layers and emissive dopants. The compound is also used in materials science due to its robust stability and predictable reactivity under standard conditions.

Market Size, Supply & Pricing

Global pharmaceutical demand, particularly for Macitentan API, is the primary driver of the market. The global Macitentan API market was valued at approximately USD 260‑280 million in 2024 and is projected to grow at a CAGR of 6‑8% through 2032. The Chinese PAH market, a key growth region, is expanding at an even higher rate (CAGR 8‑10%).

The major international suppliers include TCI Chemicals (≥98% purity, product code B4950, research and bulk grades), BenchChem (key starting material for Macitentan), BOC Sciences, Biozol (store at –20°C), CymitQuimica, AK Scientific (purity 98%, GC), Biozol, Biosynth Carbosynth, Apollo Scientific, Toronto Research Chemicals (TRC), MolCore, Combi‑Blocks and others. Chinese manufacturers dominate the global supply for this intermediate, with annual capacities in the multi‑metric‑ton range and production lines dedicated exclusively to pharmaceutical‑grade tri‑halogenated pyrimidines. The compound is typically supplied with purity ranging from 98% to ≥99% (GC), as a white to light‑yellow crystalline powder with a melting point of 97‑102 °C and a molecular weight of 303.97 g/mol.

Pricing data from major Chinese suppliers: for 98‑99% purity grades, unit prices range from approximately USD 4‑6 per gram for R&D quantities (1‑25 g), USD 2.50‑3.50 per gram for pilot scales (100‑500 g) and USD 1.00‑2.00 per gram for bulk industrial orders (1‑25 kg). TCI Shanghai pricing (domestic China, excluding VAT) for the product (purity >98.0% GC) is as follows: ¥185/1 g, ¥620/5 g and ¥2,500/25 g. International suppliers generally price R&D‑scale quantities at USD 10‑20 per gram for 1‑5 g and USD 5‑10 per gram for 10‑25 g, while bulk industrial pricing is available upon request from manufacturers and dedicated API‑intermediate suppliers.

Regional Market Dynamics

Global demand for 5‑(4‑bromophenyl)‑4,6‑dichloropyrimidine follows a clear regional pattern: Asia‑Pacific is the largest and fastest‑growing region for production and intermediate supply, North America and Europe lead in high‑purity pharmaceutical consumption, and Latin America & Middle East/Africa are emerging generic manufacturing hubs.

Asia‑Pacific, and China in particular, is the global manufacturing hub for tri‑halogenated pyrimidine intermediates. Chinese manufacturers have optimised large‑scale SNAr and purification processes, producing high‑purity 5‑(4‑bromophenyl)‑4,6‑dichloropyrimidine at highly competitive prices. India‘s rapidly expanding generic Macitentan API sector (with several ANDA approvals pending or recently granted) drives significant volume demand.

North America and Europe command the largest share of high‑purity R&D and commercial consumption (≥99%), driven by the highest concentration of Macitentan API manufacturing (brand and generic), PAH drug discovery programmes and advanced agrochemical innovation centres. Customer requirements in these regions are stringent: purity ≥99%, full traceability, ICH Q3D compliance for heavy metals, full impurity profiling (including residual solvents by GC‑headspace and related substances by HPLC‑UV) and cGMP documentation for pharmaceutical use. The compound‘s role as a KSM‑I impurity reference standard for ANDA filings further increases the demand for high‑purity, fully characterized material in regulated markets. Japan and the Republic of Korea demand ultra‑high‑purity grades for advanced pharmaceutical development and high‑performance OLED fabrication.

Storage, Stability & Regulatory Considerations

5‑(4‑Bromophenyl)‑4,6‑dichloropyrimidine (CAS 146533‑41‑7) should be stored below 15 °C in a tightly sealed, dry, light‑protected container, away from strong oxidizing agents and strong bases, under an inert gas (nitrogen or argon). The compound is light‑sensitive. It is stable for up to three years when stored as a powder at –20 °C and for up to two years at 2‑8 °C; solutions in DMSO are stable for up to one year at –80 °C. GHS hazard classification: H315 (Causes skin irritation), H317 (May cause an allergic skin reaction) and H319 (Causes serious eye irritation). Precautionary measures: P264 (wash skin thoroughly after handling), P280 (wear protective gloves/eye protection/face protection). For users targeting the Russian market, XinChem provides full Russian‑language Safety Data Sheets (MSDS) compliant with EAEU Technical Regulation 041/2017 (On Safety of Chemicals) and can support customers with REACH‑like dossiers required for Customs Union importation. In the European Union, the compound is subject to REACH regulations; importers and manufacturers must provide Safety Data Sheets (SDS). In the United States, it is regulated under TSCA as a research chemical; for pharmaceutical API use, adherence to cGMP guidelines (21 CFR Parts 210/211) is required. In China, the compound is listed in the Inventory of Existing Chemical Substances (IECSC) with customs HS Code 29335990 (Compounds containing an unfused pyrimidine ring) and requires safety production licences for manufacturing facilities.

Future Outlook

The market outlook for 5‑(4‑bromophenyl)‑4,6‑dichloropyrimidine is tied to four core drivers: (1) the continued expansion of the Macitentan API market, driven by the global adoption of Opsumit® and generic entry into PAH and IPF treatment; (2) the rapid growth of the agrochemical sector, with heterocyclic pyrimidine scaffolds as key building blocks for next‑generation herbicides and fungicides; (3) the expansion of Asian CRO/CDMO sectors supplying intermediates to global pharmaceutical and agrochemical companies; and (4) the increasing adoption of the compound in OLED fabrication and advanced polymer synthesis.

Shanghai XinChem Co., Ltd. (XinChem)

As a world‑leading supplier of pharmaceutical intermediates and heterocyclic building blocks, Shanghai XinChem Co., Ltd. (XinChem) has always focused on the innovative needs of the Macitentan API manufacturing, PAH drug discovery, agrochemical development and advanced material industries. Relying on core advantages in tri‑halogenated pyrimidine synthesis, purification and rigorous quality assurance, we provide high‑quality 5‑(4‑Bromophenyl)‑4,6‑dichloropyrimidine (CAS 146533‑41‑7) to global customers.

1. Technical Advantages

High Purity & Consistency: Our product achieves purity ≥98% (GC), white to light‑yellow crystalline powder, molecular weight 303.97 g/mol, melting point 97‑102 °C, MDL MFCD08277258, and moisture <0.5% (KF titration).
Low Impurity Profile: Strict control of residual solvents (<0.5% total), heavy metals (≤10 ppm, ICH Q3D compliant), and related substances by HPLC‑UV ensures high synthetic performance for Macitentan API, agrochemical and advanced material manufacturing.
Pharmaceutical‑Grade Quality: The compound is tested for full ICH Q3C (residual solvents), ICH Q3D (heavy metals) and USP residual solvents, and is available with DMF support for Macitentan ANDA filings. It is supplied as a KSM‑I impurity reference standard with detailed characterisation data compliant with regulatory guidelines.
Batch‑to‑Batch Uniformity: Rigorous analytical testing (GC, HPLC, NMR, LC‑MS, heavy metals by ICP‑MS, residual solvents by GC‑headspace, Karl Fischer titration) guarantees consistent quality and reproducible yields across all production lots.

2. Product Advantages

The Key Starting Material for Macitentan API: The unequivocal key building block for Macitentan (Opsumit®), used directly in FDA‑approved PAH and IPF therapeutics. Also serves as a KSM‑I impurity reference standard for AMD, AMV and QC in ANDA submissions.
Versatile Tri‑Halogenated Scaffold: The 4‑ and 6‑chlorine atoms enable sequential SNAr reactions; the 5‑(4‑bromophenyl) group provides an additional handle for cross‑coupling chemistry (Suzuki‑Mori, Buchwald‑Hartwig). This orthogonal functionalisation platform enables medicinal chemists to rapidly generate libraries of substituted pyrimidine derivatives for SAR exploration in agrochemical and drug discovery programmes.
Multiple High‑Value Applications: Directly used as a pharmaceutical intermediate for Macitentan, agrochemical intermediate for herbicides and fungicides, anticancer and antiviral drug discovery building block, and OLED/advanced material precursor.
Flexible Packaging Options: 1 g, 5 g, 10 g, 25 g, 50 g, 100 g, 500 g, 1 kg glass bottles/HDPE containers (R&D/pilot); 5 kg, 10 kg, 25 kg, 50 kg fiber drums (industrial). Full custom packaging available for pharmaceutical, agrochemical and advanced material campaigns. For the Russian market, XinChem provides full Russian‑language SDS and customs documentation.
Reliable Supply Chain: Annual capacity in the multi‑metric‑ton range, with dedicated temperature‑controlled warehousing (below 15 °C, under inert gas, dry, light‑protected, sealed containers) and just‑in‑time delivery capabilities.

3. Application Fields

Pharmaceutical Intermediates: Key building block for Macitentan API (Opsumit®) for PAH and IPF; generic Macitentan API manufacturing for ANDA filings; KSM‑I impurity reference standard for AMD, AMV and QC.
Agrochemical Intermediates: Herbicide synthesis, fungicide synthesis, crop protection formulations, triazole derivative synthesis with antifungal activity.
Anticancer & Antiviral Drug Discovery: Anticancer agents, antiviral agents, kinase inhibitors, fragment‑based drug discovery (FBDD), SAR libraries, substituted pyrimidine analogues prepared via Suzuki‑Miyaura cross‑coupling.
Advanced Materials & OLED: OLED electron‑transport layers, emissive dopants, high‑performance polymers, organic semiconductors, optoelectronic materials.
CRO/CDMO Custom Synthesis: Essential custom‑synthesised intermediate for medicinal chemistry outsourcing, hit‑to‑lead optimisation and preclinical toxicology studies.

4. Service Support
Our technical team provides full impurity profiling (GC purity, HPLC‑UV related substances, residual solvents by GC‑headspace, heavy metals by ICP‑MS, LC‑MS identity confirmation), custom purification to any desired specification, and complete regulatory documentation (Certificate of Analysis, Technical Data Sheet, Safety Data Sheet, REACH compliance, TSCA certification, DMF support for Macitentan ANDA customers). For the Russian market, we provide full Russian‑language SDS (MSDS) compliant with EAEU Technical Regulation 041/2017 and can support customers with REACH‑like dossiers required for Customs Union importation. We also offer custom synthesis of tri‑halogenated pyrimidine derivatives, cold‑chain logistics, and just‑in‑time delivery.

5. Why Choose XinChem

Professionalism: 20 + years in the pharmaceutical intermediate, heterocyclic chemistry and fine chemical industries.
Flexibility: Tailored to customer purity specifications, packaging sizes, regulatory documentation requirements, and Russian import compliance needs.
Cost‑effectiveness: High purity at competitive industrial pricing.

Post time: Jun-07-2026

The Critical Tri‑Halogenated Pyrimidine Scaffold for Macitentan, Next‑Gen Agrochemicals and Targeted Drug Discovery: 5-(4-Bromophenyl)-4,6-dichloropyrimidine (CAS 146533-41-7)