INOSITOL 87-89-7 MANUFACTURER EXPORTER MEDIOCON INC

 

6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-oneManufacturer  Supplier Exporter MEDIOCON INC..

Name: 6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one

CAS No:  76536-66-8                                                                                                    Molecular Weight: 391.47 g/mol

Molecular formula:  C₂₃H₂₅N_3O3

·       Synonyms:                                                                                                                                                                 2-(Mesitylamino)-9,10-dimethoxy-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one

·       9,10-Dimethoxy-2-(2,4,6-trimethylanilino)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one

·       4H-Pyrimido[6,1-a]isoquinolin-4-one, 6,7-dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-

·       9,10-Dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one 

Appearance:  white to off-white solid powder

·       Solubility :                                                                                                                                                                                      Water Solubility: Practically insoluble; predicted at approximately 0.02 mg/mL.

·       Organic Solvents:

o   DMSO & DMF: This compound is typically slightly soluble in Dimethyl Sulfoxide (DMSO) and Dimethylformamide (DMF).

o   Methanol & Ethanol: Exhibits very low solubility, often requiring heating or high volumes of solvent for dissolution.

o   Chlorinated Solvents: It generally shows better solubility in solvents like Chloroform or Dichloromethane due to its organic structure, though specific mg/mL data is often proprietary. 

Factors Influencing Solubility

·       Salt Form: The hydrochloride salt version (CAS 2314643-98-4) is available and specifically used to enhance its solubility and stability for laboratory applications.

·       Lipophilicity: With a calculated LogP of approximately 3.12 to 3.27, the molecule has a significant preference for lipid-like environments over water.

·       Thermodynamic State: As a crystalline solid, its solubility can vary based on its polymorphic form (I, II, or III), which is a critical factor currently being studied for drug formulation as of 2025. 

Use :

As of 2025, the primary uses for 6,7-dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one (CAS 76536-66-8) are centered on its role in the pharmaceutical lifecycle of Ensifentrine (brand name Ohtuvayre), a dual PDE3/PDE4 inhibitor. 

1. Key Pharmaceutical Intermediate

The compound is an essential building block (Intermediate ENS-4) in the chemical synthesis of Ensifentrine. 

·       Manufacturing: It is used by chemical manufacturers to produce the final active pharmaceutical ingredient (API) for the treatment of Chronic Obstructive Pulmonary Disease (COPD).

·       Regulatory Submissions: High-purity batches are required for meeting industrial standards (typically 98% purity) in pharmaceutical manufacturing processes. 

2. Analytical Reference Standard (Impurity Testing)

The compound is utilized as a reference standard in quality control and analytical research. 

·       Impurity Profiling: It is specifically identified as Ensifentrine Des-ethyl Impurity. Labs use it to detect, identify, and quantify impurities in commercial batches of Ensifentrine to ensure patient safety and consistency.

·       Method Validation: It is essential for the development and validation of analytical methods (such as HPLC) required for regulatory filings like Abbreviated New Drug Applications (ANDA). 

3. Pharmaceutical Research

Beyond its direct role in Ensifentrine production, the molecule is studied for its own potential biological activities:

·       Cardiovascular Research: Patents suggest applications in treating cardiovascular disorders, including ischemic or atherosclerotic diseases.

·       Respiratory Therapy Exploration: As a precursor to modern PDE inhibitors, it is used in ongoing research to explore new treatments for other respiratory conditions like asthma and cystic fibrosis.

·       Medicinal Chemistry Building Block: It is categorized as a "Fine Chemical" used by researchers to synthesize other pyrimido[6, 1-a]isoquinoline derivatives with various therapeutic potentials. 

How is  6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one manufactured by MEDIOCON INC. Synthesized?

As of 2025,

Mediocon Inc. manufactures 6,7-dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one (CAS 76536-66-8) as a specialized pharmaceutical intermediate known as ENS-4. This compound is a vital precursor in the production of Ensifentrine (brand name Ohtuvayre), a dual PDE3/PDE4 inhibitor for COPD treatment. 

While the exact internal protocol of Mediocon Inc. is proprietary, the industry-standard synthesis for this specific intermediate follows a recognized three-step sequence: 

Standard Synthesis Route for ENS-4 

1. Preparation of the Barbituric Acid Intermediate:
   The synthesis begins with 1-(3,4-dimethoxyphenethyl)urea (CAS 25017-47-4), which is reacted with diethyl malonate or a similar reagent to form a barbituric acid derivative.
2. Chlorination:
   The resulting barbituric acid intermediate is chlorinated, typically using phosphorus oxychloride (POCl3cap P cap O cap C l sub 3𝑃𝑂𝐶𝑙3), to produce 2-chloro-9,10-dimethoxy-6,7-dihydro-4H-pyrimido[6,1-a]isoquinolin-4-one (CAS75535-96-5).
3. Nucleophilic Substitution (Final Step for ENS-4):
   The chlorinated intermediate undergoes a substitution reaction with 2,4,6-trimethylaniline (also known as mesitylamine) to yield the final white to off-white solid powder, ENS-4. 

Mediocon Inc. Manufacturing Profile 

• Location: Mediocon Inc. operates out of its facility in Aurangabad, Maharashtra, India.
• Quality Standards: The compound is typically manufactured at a purity level of ≥is greater than or equal to ≥98-99% by HPLC to meet the rigorous requirements of API synthesis.
• Packaging: It is available in commercial scales, often packed in 25kg fiber drums or specialized bags depending on procurement needs. 

Mediocon Inc. lists this compound as a key part of their Intermediates Product List, supporting the global supply chain for modern respiratory therapies. 

                                                                                                                                                                            What are the effects And Side effects of 6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one Manufactured by MEDIOCON INC.?

As of 2025, 6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one (also known as ENS-4) is an industrial chemical intermediate used solely in the manufacture of the drug Ensifentrine (brand name Ohtuvayre).

Because it is a chemical intermediate and not a final medication, its direct physiological effects on humans have not been clinically tested. Instead, the effects and side effects are typically described based on Ensifentrine, the final active drug it helps produce.

1. Therapeutic Effects (as part of Ensifentrine)

Ensifentrine is a first-in-class dual inhibitor of the PDE3 and PDE4 enzymes, providing both bronchodilator and non-steroidal anti-inflammatory effects. 

·       Improved Lung Function: Increases forced expiratory volume (FEV1), making it easier to breathe for patients with moderate to severe COPD.

·       Symptom Reduction: Significantly reduces respiratory symptoms such as shortness of breath (dyspnea), wheezing, and chest tightness.

·       Exacerbation Control: Clinical trials demonstrated a 42% reduction in the rate of moderate-to-severe COPD flare-ups over 24 weeks. 

2. Common Side Effects

In large-scale clinical trials (ENHANCE-1 and ENHANCE-2), the most common adverse reactions reported by at least 1% of patients were: 

·       Back Pain (1.8%)

·       High Blood Pressure (Hypertension) (1.7%)

·       Urinary Tract Infection (Bladder infection) (1.3%)

·       Diarrhea (1.0%)

3. Serious Side Effects

While rare, the following serious conditions have been associated with its use: 

·       Paradoxical Bronchospasm: A sudden, life-threatening tightening of the airways immediately after inhalation.

·       Psychiatric Events: Increased risk of mental health changes, including insomnia, anxiety, depression, and suicidal thoughts or behaviors.

·       Severe Allergic Reactions: Symptoms may include swelling of the face/throat, hives, racing heart, or severe dizziness. 

4. Chemical Safety (ENS-4 Intermediate)

As a raw chemical manufactured by entities like Mediocon Inc., ENS-4 itself carries industrial safety warnings for laboratory and manufacturing environments: 

·       Irritation: Causes skin and respiratory tract irritation.

·       Organ Damage: May cause damage to organs through prolonged or repeated exposure.

·       Handling: Must be handled with standard PPE (gloves, goggles) in controlled industrial settings.

Disclaimer: This compound is an intermediate for pharmaceutical manufacturing. It is not for direct human consumption in its raw form.

How is 6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one    Manufactured by MEDIOCON INC Tested Qualitatively?

As of 2025,

Mediocon Inc., located in Aurangabad, India, employs rigorous qualitative testing protocols for 6,7-dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one (ENS-4) to ensure it meets pharmaceutical-grade specifications (typically ≥ is greater than or equal to ≥98% purity). 

The qualitative testing (identity and characterization) for this intermediate generally includes the following standard laboratory techniques: 

1. Spectroscopic Identification (Primary Identity) 

To confirm the chemical structure and molecular arrangement, the following tests are performed: 

• Proton Nuclear Magnetic Resonance (¹H-NMR): Used to verify the specific proton environment, confirming the presence of the dimethoxy groups and the trimethylphenyl (mesityl) ring.
• Fourier Transform Infrared (FTIR) Spectroscopy: Identifies characteristic functional groups, such as the carbonyl (C=Ocap C equals cap O𝐶=𝑂) group in the pyrimidoisoquinolinone ring and the secondary amine (NHcap N cap H𝑁𝐻) bond.
• Mass Spectrometry (MS): Confirms the molecular weight of approximately 391.47 g/mol by identifying the molecular ion peak. 

2. Chromatographic Fingerprinting 

• HPLC (Retention Time): The most critical qualitative test. The sample's retention time is compared against a qualified reference standard. A match in retention time under validated conditions (specific column, mobile phase, and pH) confirms the identity of the batch.
• TLC (Thin Layer Chromatography): A simpler, visual qualitative check used during the manufacturing process to confirm the absence of starting materials (like mesitylamine) and the presence of the desired product based on Rfcap R sub f𝑅𝑓values. 

3. Physical Property Verification 

• Appearance: Visual inspection must confirm a white to off-white solid powder.
• Melting Point: Since ENS-4 is a crystalline solid, its melting point (typically high, often >250∘Cis greater than 250 raised to the composed with power cap C >250∘𝐶 for this class) is measured to verify purity and polymorphic consistency.
• Solubility Testing: Verified qualitatively by observing dissolution in organic solvents like DMSO or Dichloromethane and confirming its insolubility in water. 

4. Impurity Profiling 

While primarily quantitative, these tests provide qualitative assurance that specific synthesis byproducts are absent: 

• Residual Solvent Analysis: Using Gas Chromatography (GC) to ensure that solvents like POCl3cap P cap O cap C l sub 3𝑃𝑂𝐶𝑙3 or ethanol used in synthesis are removed.
• Elemental Impurity Testing: Ensuring the absence of heavy metals through ICP-MS, which is a requirement for intermediates intended for final API (Ensifentrine) production. 

Mediocon Inc. issues a Certificate of Analysis (CoA) for each batch, summarizing these qualitative and quantitative results to ensure compliance with cGMP standards. 

Which tests are performed on  6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one   Manufactured by  MEDIOCON INC.?

Mediocon Inc., located in Aurangabad, India, manufactures

6,7-dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one (also known as ENS-4) as a high-purity pharmaceutical intermediate. 

As of 2025, to ensure this compound meets the rigorous standards required for synthesis into the active drug Ensifentrine, Mediocon Inc. performs the following tests: 

1. Identity and Structural Verification 

These qualitative tests confirm that the chemical structure matches the intended molecule (CAS No. 76536-66-8): 

• Proton & Carbon NMR (¹H & ¹³C NMR): Confirms the arrangement of the dimethoxy and trimethylphenyl (mesityl) groups.
• Mass Spectrometry (MS): Verifies the molecular weight is approximately 391.46 - 391.5 g/mol.
• FT-IR Spectroscopy: Identifies characteristic functional groups, such as the carbonyl (C=Ocap C equals cap O𝐶=𝑂) group in the pyrimidoisoquinolinone ring.
• X-Ray Diffraction (PXRD/SCXRD): Used for solid-state characterization to identify specific polymorphic forms (e.g., Form I, II, or III), which are critical for solubility and stability. 

2. Purity and Composition Testing 

These quantitative tests ensure the product is free from harmful contaminants: 

• HPLC Purity: Typically certified at a specification of ≥is greater than or equal to ≥ 98-99% purity.
• Impurity Profiling: Monitors for specific byproducts, such as the "Ensifentrine Des-ethyl Impurity" or residual starting materials.
• Residual Solvent Analysis: Ensures that solvents used in the manufacturing process (like phosphorus oxychloride or ethanol) are within safe regulatory limits. 

3. Physical Property Analysis 

• Appearance: Visual confirmation of a white to off-white solid powder.
• Thermal Analysis (DSC/TGA): Differential Scanning Calorimetry and Thermogravimetric Analysis are used to determine the melting point and thermal stability.
• Solubility Testing: Verified against specific solvent profiles (e.g., DMSO) to ensure consistency for further pharmaceutical processing. 

4. Compliance and Documentation 

Every batch is typically accompanied by a Certificate of Analysis (CoA) that summarizes these results, ensuring the product is ready for use in GMP-compliant pharmaceutical manufacturing. 

What are the challenges in Manufacturing of 6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one Manufactured by MEDIOCON INC?

Manufacturing

6,7-dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one (ENS-4), especially at industrial scales by manufacturers like Mediocon Inc., involves several technical and logistical challenges. 

1. Complex Multistep Synthesis 

The production of ENS-4 requires a sophisticated multistep organic synthesis, typically starting from 1-(3,4-dimethoxyphenethyl)urea. 

• Ring Closure: A major challenge is the efficient formation of the complex pyrimido[6, 1-a]isoquinoline skeleton, which often requires precise control over condensation and cyclization reactions.
• Steric Hindrance: Introducing the mesitylamino group (a bulky 2,4,6-trimethylphenylamino moiety) into the 2-position of the ring system can be difficult due to steric hindrance, requiring optimized reaction temperatures and catalyst selection. 

2. Polymorphism and Physical Stability 

The molecule can exist in multiple solid forms (polymorphs), specifically Form I, Form II, and Form III. 

• Form Control: Maintaining the correct polymorphic form is a significant manufacturing hurdle. Form II and III can spontaneously convert back to Form I under certain conditions, affecting the intermediate's solubility and how it reacts in the final API (Ensifentrine) synthesis.
• Solubility Issues: As a highly lipophilic compound (logP ~3.5), it is practically insoluble in water, which complicates standard aqueous-based purification methods. 

3. High Purity Requirements 

As a key intermediate for the respiratory drug Ensifentrine, ENS-4 must meet extreme purity standards (typically ≥ is greater than or equal to ≥98-99%). 

• Impurity Removal: Removing closely related synthesis byproducts, such as the "Ensifentrine Des-ethyl Impurity," requires high-resolution chromatography and precise crystallization techniques.
• Residual Halogens: Since synthesis often involves chlorination (using reagents like POCl3cap P cap O cap C l sub 3𝑃𝑂𝐶𝑙3), ensuring that no residual corrosive halogens remain in the final powder is a critical quality control challenge. 

4. Regulatory and Safety Compliance 

For a company like Mediocon Inc., maintaining global supply chains in 2025 involves significant regulatory overhead: 

• Compliance Documentation: Providing a wide range of certifications (WHO-GMP, ISO 9001:2015, Halal, Kosher) and detailed technical packages (USDMF, EDMF) for regulated markets like the US and EU is a constant operational challenge.
• Hazardous Reagents: The use of hazardous chemicals in the cyclization and chlorination steps requires specialized containment and waste management systems. 

What is the Packing for 6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one Manufactured by MEDIOCON INC.?

As of 2025, Mediocon Inc., located in Aurangabad, India, provides standardized industrial packaging for the pharmaceutical intermediate 6,7-dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one (ENS-4).

Standard Packaging Specifications

·       Packaging Type: Typically packed in fiber drums with double-layered low-density polyethylene (LDPE) liners to ensure product integrity and moisture protection.

·       Unit Size: The standard bulk packaging unit is 25 kg per drum.

·       Inner Lining: Bags are often vacuum-sealed or flushed with an inert gas like nitrogen if high purity is required, to prevent oxidation during transit.

·       Small Scale: For research and development (R&D) or laboratory use, the compound may be available in smaller quantities such as 1 kg or 5 kg in high-density polyethylene (HDPE) bottles or specialized aluminum foil bags. 

Storage and Handling

To maintain the quality of the white to off-white powder, the following storage guidelines are mandated on the packaging labels:

·       Temperature: Store in a cool, dry place, typically at room temperature or refrigerated (2–8°C) depending on the batch's specific stability profile.

·       Protection: Keep the container tightly closed and protected from direct sunlight and humidity.

·       Compliance: All packaging from Mediocon Inc. is designed to meet international safety and regulatory standards, including WHO-GMP and ISO 9001:2015 requirements. 

 

What is shelf life Of 6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one   Manufactured by MEDIOCON INC.? 

As of 2025, the standard shelf life for

6,7-dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one (ENS-4) manufactured by Mediocon Inc. is typically 24 months (2 years) from the date of manufacture. 

Key Factors for Maintaining Shelf Life: 

To ensure the compound remains stable and meets its purity specifications (typically ≥ is greater than or equal to

≥99%) throughout this period, the following storage conditions are required: 

• Temperature Control: It should be stored in a cool, dry place. While stable at controlled room temperature, many pharmaceutical manufacturers recommend storage at 2°C to 8°C (refrigerated) for long-term stability of high-purity batches.
• Protection from Light: The compound is sensitive to prolonged light exposure, which can cause discoloration of the white/off-white powder. It must be kept in light-resistant containers.
• Atmospheric Integrity: The packaging (usually double LDPE liners inside a fiber drum) must remain tightly sealed to prevent moisture absorption and oxidation. 

Re-test Date: 

After the initial 24-month period, the material is not necessarily expired but must undergo re-testing. If the HPLC purity and physical characteristics still meet the original Certificate of Analysis (CoA) specifications, the shelf life may be extended for an additional 6 to 12 months. 

Note: Always refer to the specific Certificate of Analysis (CoA) provided with your batch from Mediocon Inc., as the exact shelf life and re-test date are determined by real-time stability studies specific to that production lot.

recommendations to ensure the integrity of the chemical over time. 

Where can 6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one   Manufactured by MEDIOCON INC. are procured?

6,7-Dihydro-9,10-dimethoxy-2-[(2,4,6-trimethylphenyl)amino]-4H-pyrimido[6,1-a]isoquinolin-4-one Manufactured by Mediocon Inc . can be procured from various sources, depending on your location and requirements. Here are some options:

FOR API INTERMEDIATES

FOR API MEDIOCON INC

Add: B-2, ARCH SARTHAK BUILDING, N-7 CIDCO

CHATRAPATI SAMBHAJI NAGAR-431003, MAHARASHTRA, INDIA

Mob/Whatsapp No: +91-8007719681, +91-9309999757, +91-9834786939

Sales Department: Email: sales@mediocon.com

Purchase Department: Email: purchase@mediocon.com

Marketing Department: Email: mktg@mediocon.com

HR Department: Email: hr@mediocon.com

Accounts Department: Email: accounts@mediocon.com          

Factory Address: Plot No 11, Shendra MIDC, Aurangabad-431154, Maharashtra, India Website:  www.mediocon.com 

Email id:info@mediocon.com           

GST No: 27DHUPM2366D1ZZ

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