Synthesis Process of Vilisegua API: Optimized Mass Production of Key Pyrazole Heterocyclic Intermediates (CAS 1350653-20-1)

Abstract

global demand for innovative drugs for chronic heart failure continues to expand, and Vilisiseiga (CAS 1350653-20-1) attracts a large number of CDMO and API companies to lay out generic drug development. As the first sGC stimulator, its large-scale preparation is highly dependent on high-quality fluoropyrazole intermediates. Ethyl 5-amino -1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate (CAS 256504-39-9) and ethyl 5-fluoro -1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b] pyridine-3-carboxylate (CAS 1361232-72-5) constitute the current industrial mainstream linear synthesis routes. This paper focuses on the difficulties of the synthesis process, the structural advantages of the two core intermediates, and the quality control standards, and provides a stable batch procurement plan for the research and development and commercial production of pharmaceutical companies.

1. Market Overview and Villisigua CAS 1350653-20-1 Therapeutic Positioning

1.1 basic parameters

table

1.2 therapeutic value and clinical orientation

viliciga acts on the NO-sGC-cGMP signaling pathway to direct the core pathological mechanism of heart failure with reduced ejection fraction (HFrEF). Unlike traditional heart failure drugs, efficacy is independent of endogenous nitric oxide levels in the body.

VICTORIA Phase III clinical confirmed that standard therapy combined with velicequa can significantly reduce the risk of cardiovascular death and heart failure rehospitalization in patients with stable high-risk heart failure. The unique mechanism of action makes it an important choice for combination regimens for severe heart failure.

With the start-up of generic drug projects in various countries, the stable acquisition of qualified synthetic blocks has become a key bottleneck for enterprises to promote the Villesigua API project.

2. process analysis: two core blocks supporting the synthesis of Vilisiga

there are many synthetic routes, but most of the routes have long reaction steps, harsh conditions, difficult separation of impurities and low total yield. Relying on the linear route of CAS 256504-39-9 and CAS 1361232-72-5, it is the most suitable process scheme for scale-up production.

2.1 Ethyl 5-amino -1-(2-fluorobenzyl)-1H-pyrazole-3-carboxylate CAS 256504-39-9

parameter Table

table

process value

the amino pyrazole ester comes with the necessary 2-fluorobenzyl structure of the target molecule, which can save the additional N-benzyl chemical process downstream, and greatly reduce the side reaction and derivative impurities.

After intramolecular cycliation and selective fluorination, it can be converted into advanced intermediate CAS 1361232-72-5. It is suitable for CRO pre-route exploration and small-scale process verification, and can provide small batch samples for scientific research separately.

2.2 Ethyl 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo [3,4-b] pyridine-3-carboxylate CAS 1361232-72-5

parameter Table

table

process value

the intramolecular pyrazolopyridine fused ring skeleton is completely matched with the villisiquat carbon skeleton, and API can be obtained by three steps of ester hydrolysis, cyanation and pyrimidine condensation.

Intermediate quality directly determines the late purification pressure. Insufficient purity of raw materials can significantly increase refining costs, and there is also a risk of genotoxicity caused by impurities, hindering subsequent DMF and overseas declarations.

2.3 synthetic route sequence

CAS 256504-39-9 → Cyclofluorination → CAS 1361232-72-5 → Hydrolysis, Cyanation, Pyrimidine Condensation → Viliseigon API CAS 1350653-20-1

risks to be Focused on Avoiding in 3. Procurement of Vilixiga Intermediates

CDMO and API manufacturers focus on CAS 256504-39-9 and CAS 1361232-72-5 when purchasing:

1. the single impurity of the intermediate exceeds the standard, and the impurity is transferred to the finished product API, resulting in non-compliance of registration;

2. poor batch stability, resulting in small test to pilot, commercial production yield fluctuations;

3. lack of complete analysis data, unable to meet the requirements of overseas declaration materials.

4.

4. our supply plan for Viliseb heterocyclic intermediates.

• Exclusive fluorine heterocyclic production line independent synthesis, to ensure stable quality between batches;

• flexible packaging: 10g scientific research samples to tons of industrial batch can be supplied;

• full set of analysis documents: COA, nuclear magnetic resonance, liquid phase, mass spectrometry, can cooperate with overseas registration;

• mature export logistics, thermal heterocyclic products to provide cold chain vacuum packaging, services in Europe and the United States, Asia Pacific pharmaceutical companies.

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5. Frequently Asked Questions FAQ

q1: Why is this dual-intermediate route preferred for the synthesis of velisigua?

A: Compared with other convergent routes, this route has fewer high-risk reactions, simple impurity traceability, mild reaction conditions and obvious overall yield advantages, and is the preferred process for commercial amplification.

Q2: Can CAS256504-39-9 and 1361232-72-5 be purchased separately without placing orders in complete sets?

A: They can be purchased separately. CAS256504-39-9 can also be used for the research and development of other pyrazole sGC agonists.

Q3: What information can you provide to support API declaration?

A: Conventionally provide COA, spectrum, MSDS and process description; Relevant technical data on customized impurity research can be negotiated.

Q4: Do the two fluorinated heterocyclic intermediates have to be transported in the cold chain?

A: Vacuum cold chain packaging is recommended for long-distance ocean transportation to prevent product discoloration and purity decline; We provide standardized temperature-controlled export packaging solutions.

6. Conclusion & Transformation Guidance

the global velisigua generic drug project continues to advance, stable access to high-quality heterocyclic intermediates, become the core competitiveness of API enterprises.

Our company has a long-term stable supply of high-purity CAS 256504-39-9 and CAS 1361232-72-5, which are suitable for the full-stage production requirements of laboratory process development, pilot scale-up and commercial API.

Welcome to contact technical sales for sample COA, quotation and detailed technical information.