Pyrazolopyrimidine Ester Crystal Form for Stable BTK Prodrug Storage
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Solution Overview
Problem
The amorphous form of the pyrazolopyrimidine ester compound used as a BTK inhibitor prodrug exhibits poor stability and susceptibility to heat and moisture, leading to significant degradation during storage, which complicates its handling and storage.
Innovation Solution
Development of a crystalline form (Form I) of the pyrazolopyrimidine ester compound with specific XRPD, DSC, and IR characteristics, prepared through methods involving solvent mixing and stirring, which enhances stability and allows long-term storage without special environmental conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If the compound is synthesized as an amorphous form, then the synthesis process is simpler, but the stability and storage properties deteriorate significantly
Solution Approach 1:
The patent transforms the compound from amorphous state to crystalline state (Form I), changing its physical parameters to achieve superior stability while maintaining synthetic accessibility through established chemical routes
2Ease of operation
If the amorphous compound is stored under regular conditions, then storage requirements are simpler, but degradation occurs rapidly
Solution Approach 1:
By changing the physical state from amorphous to crystalline (Form I), the compound achieves enhanced stability that allows storage under regular conditions without significant degradation, resolving the contradiction between storage simplicity and compound integrity
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 crystalline form (Form I) demonstrates improved stability, allowing for long-term storage under regular conditions and maintaining purity, with lower degradation rates compared to the amorphous form.
Implementation Method 1
which has three or more (preferably four or more, five or more, six or more, seven or more, or eight) characteristic peaks expressed in degrees 2θ at 11.26°, 14.03°, 14.80°, 17.07°, 19.78°, 21.21°, 22.390 and 23.850 in its X-ray powder diffraction (XRPD) pattern
Implementation Method 2
The crystalline form Form I is characterized by the DSC and TGA curves as shown in FIG. 2
Implementation Method 3
In thermogravimetric analysis (TGA), the crystalline form Form I exhibits no significant weight loss before degradation
Implementation Method 4
Additionally, the crystalline form Form I has characteristic absorption bands at wavenumbers of 493, 519, 587, 609, 676, 692, 759, 774, 794, 808, 869, 895, 934, 963, 1000, 1027, 1073, 1102, 1134, 1158, 1229, 1342, 1382, 1448, 1490, 1523, 1559, 1589, 1645, 1681, 1753, 2870, 2954, 3067, 3149 and 3406 cm−1 in its infrared (IR) spectrum
Data Source
AI summary
The present invention provides a crystalline form Form I of a pyrazolopyrimidine ester compound of the structure of formula (I)This crystalline form has been characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The present invention also provides methods of preparing the crystalline form Form I of the pyrazolopyrimidine ester compound. This crystalline form allows long-term storage without special requirements in respect of temperature, light, humidity or oxygen presence and is significantly advantageous in terms of stability. Moreover, the methods involve simple steps and provide good reproducibility and excellent purity. Therefore, they have a promising prospect of extensive application.