7H-pyrrolo[2,3-d]pyrimidine Synthesis via Borane Reduction
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Solution Overview
Problem
Current methods for preparing 7H-pyrrolo[2,3-d]pyrimidine derivatives as Janus kinase (JAK) inhibitors face challenges in achieving high optical purity and scalability, particularly in large-scale synthesis due to inappropriate reactions like ozone oxidation and LAH reduction.
Innovation Solution
A process involving the preparation of a disodium salt dihydrate of a compound of formula [10] through specific steps including reduction with boron trifluoride-diethyl ether complex and borane-tetrahydrofuran complex, and subsequent reactions with organic acids and protecting group removals to obtain the 7H-pyrrolo[2,3-d]pyrimidine derivative, avoiding inappropriate reactions for scalable synthesis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional methods (ozone oxidation and LAH reduction) are used for preparing 7H-pyrrolo[2,3-d]pyrimidine derivatives, then the synthesis route is established, but the optical purity and scalability are compromised
Solution Approach 1:
The patent changes the chemical reaction parameters by replacing ozone oxidation with alternative oxidation methods and LAH reduction with alternative reduction methods that are more suitable for large-scale synthesis while maintaining or improving optical purity
Solution Approach 2:
The patent employs readily available reagents and simplifies the synthesis route by removing problematic steps, making the process more economical and scalable for industrial production
2Productivity
If ozone oxidation and LAH reduction reactions are used, then the synthesis can proceed, but the process becomes inappropriate for large-scale synthesis
Solution Approach 1:
The patent extracts and removes the problematic ozone oxidation and LAH reduction steps from the synthesis route, eliminating the reliability issues associated with these reactions while maintaining the overall synthetic pathway
Solution Approach 2:
The patent introduces intermediate compounds and alternative reaction pathways that serve as mediators to achieve the same synthetic transformation without using the unreliable ozone oxidation and LAH reduction steps
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
This method enables the preparation of 7H-pyrrolo[2,3-d]pyrimidine derivatives with high optical purity and scalability, improving the synthesis route by avoiding ozone oxidation and LAH reduction reactions, thus enhancing the synthesis efficiency and product quality.
Implementation Method 1
the step of reducing a compound of formula (10) in the presence of boron trifluoride-diethyl ether complex and borane-tetrahydrofuran complex to give a compound of formula (11)
Data Source
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AI summary
The present invention provides a method for producing a 7H-pyrrolo[2,3-d]pyrimidine derivative that is useful as a janus kinase (JAK) inhibitor; an intermediate of the 7H-pyrrolo[2,3-d]pyrimidine derivative; and a method for producing the intermediate. The present invention provides a method for producing 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]octan-1-yl]-3-oxopropanenitrile, which uses a salt of an organic acid and (3S,4R)-3-methyl-1,6-diazaspiro[3.4]octane-1-carboxylic acid benzyl.