Pyrrolo[2,3-d]Pyrimidine Crystallization for Pharmaceutical Forms

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Solution Overview

Problem

Existing manufacturing processes for N-((1S,3S)-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclobutyl)propane-1-sulfonamide lack the ability to produce crystalline forms with improved properties suitable for pharmaceutical dosage forms, particularly for oral and topical applications.

Innovation Solution

A novel process is developed to prepare crystalline and non-crystalline forms of N-((1S,3S)-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclobutyl)propane-1-sulfonamide, utilizing specific reaction conditions and reagents to achieve desired structural and diffraction patterns, enabling the production of pharmaceutical-grade compounds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If existing manufacturing processes are used, then the compound can be produced, but the crystalline form with improved properties suitable for pharmaceutical dosage forms cannot be obtained

Engineering Contradiction:
Improvecrystalline form qualityVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by modifying reaction conditions including temperature ranges (0°C to reflux), solvent systems (ethyl acetate, isopropanol, water), and pH control during the synthesis process to obtain specific crystalline forms with improved properties suitable for pharmaceutical dosage forms

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes phase transitions by controlling the crystallization process from solution to obtain distinct crystalline forms (Form I, Form II, etc.) with different properties, enabling selection of optimal forms for pharmaceutical applications based on solubility, stability, and bioavailability requirements

Inventive Principle:
Principle #36Phase transitions

2Reliability

If crystalline forms with improved properties are produced, then therapeutic efficacy is enhanced, but the manufacturing process becomes more complex

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-determining optimal reaction parameters and crystallization conditions through systematic experimentation, establishing standardized protocols that reliably produce desired crystalline forms with enhanced therapeutic efficacy while managing process complexity through predefined procedures

Inventive Principle:
Principle #10Preliminary action

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 process yields crystalline forms with enhanced properties, suitable for pharmaceutical formulations, providing improved therapeutic efficacy in treating conditions such as lupus, rheumatoid arthritis, and other autoimmune disorders.

Implementation Method 1

The present invention is directed to a process for preparing a crystalline or noncrystalline form of N-((1S,3S)-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclobutyl)propane-1-sulfonamide free base

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Data Source

PatentEP3817810B1Manufacturing process and intermediates for a pyrrolo[2,3- d]pyrimidine compound and use thereof
Publication Date: 2025.09.17 PFIZER INC
  • EP3817810B1 patent drawingFigure 1
  • EP3817810B1 patent drawingFigure 2
  • EP3817810B1 patent drawingFigure 3

AI summary

The present invention relates to a manufacturing process and intermediates for preparing a crystalline or non-crystalline form of N-((1S,3S)-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)cyclobutyl)propane-1-sulfonamide. The present invention also relates to salt forms and pharmaceutical compositions comprising the crystalline form, and to methods for use of the compound prepared from a crystalline form in the treatment of various diseases.