Tetracyclic Compound Synthesis via Safer Solvents

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Solution Overview

Problem

The existing method for manufacturing Compound (1) faces challenges such as environmental impact, safety concerns due to solvent use, and the formation of by-products and regioisomers, necessitating an improved and industrially preferable method.

Innovation Solution

A manufacturing method for Compound (1) involving a series of steps using specific solvents like dichloromethane, 1,4-dioxane, and condensing agents like N,N'-diisopropylcarbodiimide, which avoids the use of substances of very high concern and enhances reaction selectivity, reducing by-product formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If conventional solvents and condensing agents are used in the manufacturing method of Compound (1), then the reaction can proceed, but environmental impact increases and safety concerns arise

Engineering Contradiction:
Improveenvironmental impact and safetyVSAvoidmanufacturing process
Core Design Contradiction:
Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent removes harmful solvents and condensing agents from the manufacturing process. Specifically, it eliminates substances of very high concern (SVHC) by replacing them with safer alternatives, thereby extracting the harmful components while maintaining the essential reaction functionality through alternative reagents and conditions.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the chemical parameters of the reaction system by substituting conventional solvents and condensing agents with environmentally friendly alternatives. This involves modifying the reaction conditions to use different chemical substances that achieve the same synthetic outcome without the harmful side effects of the original reagents.

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If conventional manufacturing method is used, then Compound (1) can be produced, but by-products and regioisomers are formed reducing manufacturing precision

Engineering Contradiction:
Improveselectivity and by-product formationVSAvoidyield and efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent applies local quality by creating specific reaction conditions that favor the formation of the desired product at specific positions. By modifying the reaction environment and using selective reagents, the method enhances the selectivity of the cyclization reaction to occur at the intended location, reducing regioisomer formation while maintaining overall productivity.

Inventive Principle:
Principle #3Local quality

3Ease of operation

If simpler manufacturing process is adopted, then ease of operation improves, but yield and manufacturing precision may decrease

Engineering Contradiction:
Improvesimplicity of manufacturing processVSAvoidyield and purity
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent employs self-service by designing a reaction system that inherently favors the desired product formation without requiring complex intervention. The modified reaction conditions and reagents create a self-directed process where the chemistry itself guides the reaction toward the correct product, reducing the need for complex purification steps while maintaining high yield and purity.

Inventive Principle:
Principle #25Self-service

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The method provides a simple, efficient, and robust process for manufacturing Compound (1) with high yield, improved safety, and reduced environmental impact, while effectively controlling impurity levels and maintaining pharmacological properties.

Implementation Method 1

a step of manufacturing a compound represented by Formula IXa: wherein R1a wherein R1a wherein R1a wherein R1a wherein X represents a leaving group, to produce a compound represented by Formula V: wherein R1a wherein R1a wherein R1 wherein R1 and R1a by treating a compound represented by Formula VIIIb: with a condensing agent

Methodology Applied
Scientific EffectCondensation reaction:

Data Source

PatentEP3848361B1Method of producing tetracyclic compound
Publication Date: 2025.01.22 CHUGAI PHARMA CO LTD
  • EP3848361B1 patent drawingFigure 1~2
  • EP3848361B1 patent drawingFigure 3~4
  • EP3848361B1 patent drawingFigure 5~6

AI summary

This invention relates to a method for manufacturing 9-ethyl-6,6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile, and is industrially preferable, allowing an objective substance to be obtained in high yield more safely and easily than the conventional method.