Crystal form of nitrogen-containing tricyclic compound and application thereof
A compound and crystal form technology, which is applied to the crystal form of nitrogen-containing tricyclic compounds and its application field, can solve the problems of undisclosed compound microstructure, undisclosed crystal form structure, etc.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0082] Embodiment 1 The crystal form A of the compound of formula (I)
[0083] 1. Preparation of Form A
[0084] Compound 2-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)-10H-spiro[benzo[6,7] Oxazo[3,2-b]pyridine-11,1'-cyclopropane]-7-carboxylic acid (201.5 mg) was added to isopropanol (4.0 mL) and stirred under reflux to dissolve, then the heating was stopped and cooled to room temperature naturally , stirred and crystallized for 12 hours; suction filtered, and the filter cake was vacuum-dried overnight at 50° C. to obtain a white solid (120.3 mg, 59.7%).
[0085] 2. Identification of Form A
[0086] (1) Analysis and identification by Empyrean X-ray powder diffraction (XRPD): using Cu-Kα radiation, it has the following characteristic peaks represented by angle 2θ: 7.22°, 8.65°, 11.11°, 12.61°, 12.92°, 13.86°, 14.07 °,14.37°,15.94°,16.68°,17.29°,18.95°,19.90°,20.37°,20.89°,21.00°,21.60°,22.24°,22.59°,22.86°,23.32°,24.28°,24.85°, 25.29°,25.57°,26.11°,26.30°,...
Embodiment 2
[0089] Embodiment 2 The pharmacokinetic experiment of crystal form A described in the present invention
[0090] Compound (compound 2-((5-cyclopropyl-3-(2,6-dichlorophenyl) isoxazol-4-yl) methoxy) shown in formula (I) of the present invention- 10H-spiro[benzo[6,7]oxazepine[3,2-b]pyridine-11,1'-cyclopropane]-7-carboxylic acid) filled capsules of Form A for oral administration.
[0091] 8-12kg male Beagle dogs were orally administered 5 mg / kg of the test sample, 3 animals in each group. Blood was collected at 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0 and 24 hours after administration. A standard curve with an appropriate range was established according to the concentration of the sample, and the concentration of the test sample in the plasma sample was determined in the MRM mode using AB SCIEX API4000 LC-MS / MS, and quantitative analysis was performed. According to the drug concentration-time curve, the pharmacokinetic parameters were calculated using WinNonLin 6.3 software non-compar...
Embodiment 3
[0096] Embodiment 3 The stability experiment of crystal form A described in the present invention
[0097] (1) High temperature experiment : Take an appropriate amount of a batch of test products and put them into a flat weighing bottle, spread them into a thin layer with a thickness of ≤5mm, place them at 60°C for 30 days, take samples on the 5th, 10th, and 30th days, observe the color changes of the samples, and perform HPLC detection Sample purity, X-ray powder diffraction analysis structure, its high-temperature experiment X-ray powder diffraction changes are basically as follows Figure 4 shown.
[0098] (2) High humidity experiment : Take an appropriate amount of a batch of test products and put them into a flat weighing bottle, spread them into a thin layer with a thickness of ≤5mm, place them for 30 days at 25°C and RH 90%±5%, and take samples on the 5th, 10th, and 30th days. Observe the color change of the sample, detect the purity of the sample by HPLC, and anal...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More