RX-3117 Synthesis via Telescoped Continuous Process

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Solution Overview

Problem

The existing synthesis processes for RX-3117 are inefficient and costly due to the need for multiple steps and the isolation of intermediates, making large-scale production challenging, and there is a need for an improved method to reduce costs and enhance manufacturing efficiency.

Innovation Solution

A continuous process that telescopes multiple steps without isolating intermediates, optimizing reaction conditions to improve selectivity and reduce solvent use, and using alternative reagents and solvents to streamline the synthesis of RX-3117, specifically utilizing 2-methyl-tetrahydrofuran and dimethyl sulfoxide, and adjusting reaction parameters to enhance nitrogen to oxygen isomer selectivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If multiple synthesis steps with intermediate isolation are used, then product purity is improved, but manufacturing cost and time increase

Engineering Contradiction:
Improveproduct purityVSAvoidmanufacturing efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent combines multiple synthesis steps into a telescoping sequence where intermediates are not isolated but carried forward through subsequent reactions. This merging of steps eliminates repetitive isolation and purification operations, reducing manufacturing time and cost while maintaining product purity through controlled reaction conditions and selective chemistry

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The synthesis process maintains continuous useful action by avoiding interruption for intermediate isolation. Reactants and intermediates remain in solution throughout the synthesis sequence, allowing reactions to proceed continuously without breaking the productive flow, thereby enhancing manufacturing efficiency while preserving product quality

Inventive Principle:
Principle #20Continuity of useful action

2Manufacturing precision

If multiple synthesis steps with intermediate isolation are used, then product purity is improved, but manufacturing cost increases

Engineering Contradiction:
Improveproduct purityVSAvoidmanufacturing cost
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent merges multiple synthesis steps into a telescoping sequence that eliminates repetitive isolation and purification operations. This reduces the consumption of solvents, reagents, and energy required for each separation step, thereby lowering manufacturing costs while maintaining product purity through careful reaction design and selective chemistry

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The synthesis process is designed so that reaction conditions and reagent selectivity automatically favor the formation and carry-forward of desired intermediates without requiring intensive purification. The chemistry itself serves to protect and advance the desired product through selective reactions that minimize byproduct formation, reducing the need for costly purification steps

Inventive Principle:
Principle #25Self-service

3Manufacturing precision

If traditional synthesis routes are used, then product quality is maintained, but production scalability is limited

Engineering Contradiction:
Improveproduct qualityVSAvoidproduction scalability
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent combines multiple synthesis steps into a telescoping sequence that is inherently more amenable to scale-up. By eliminating repetitive isolation and purification steps, the process reduces the complexity of equipment requirements and operational oversight needed for quality control, enabling easier transition from laboratory to industrial production while maintaining product quality through controlled reaction parameters

Inventive Principle:
Principle #5Merging (Combining)

Data Source

PatentEP4008321A1Fluorocyclopentenylcytosine for treating tumour
Publication Date: 2022.06.08 OCUPHIRE PHARM INC
  • EP4008321A1 patent drawingFigure 1
  • EP4008321A1 patent drawingFigure 2
  • EP4008321A1 patent drawingFigure 3~4

AI summary

The disclosed subject matter provides methods using and kits comprising a compound of formula (I) or a hydrate, a solvate, or a pharmaceutically acceptable salt thereof. The disclosed subject matter further provides a method of treating one or more symptoms of cancer comprising administering to a subject in need thereof a compound of formula (I) and a process for preparing such.