Pyrazolylaminoquinazoline hydrobromide
A technology of hydrobromide and amino group, applied in the field of treatment, prevention or improvement of proliferative diseases, can solve problems such as immunodeficiency
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0233] Preparation of hydrobromide salt of (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanol
[0234](4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanol (260g, 0.744mol) and ethanol (2.86L) in a circle The mixture in the bottom flask was heated to reflux under nitrogen for 30 to 40 minutes, then 48% aqueous HBr (125.5 g, 0.744 mmol) was added while maintaining reflux. The mixture was cooled to 25-30°C, and the mixture was stirred at 25-30°C for 1 hour. The solid was collected by filtration, washed well with fresh ethanol (0.52 L). Dry the solid at 55°C to 65°C for 12 to 14 hours to give (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl ) methanol hydrobromide (276 g, 86%). HPLC (AUC) 99.9%.
Embodiment 2
[0236] Characterization of Form A
[0237] Through X-ray powder diffraction (XRPD), thermogravimetric analysis (TG), differential scanning calorimetry (DSC), moisture absorption analysis, hot stage microscopy and proton nuclear magnetic resonance spectroscopy ( 1 HNMR) Characterization Form A. In summary, the HBr salt of Form A is consistent with the crystalline salt of the compound of formula I, including residual solvent.
[0238] figure 1 A representative XRPD pattern of crystalline Form A is shown in . Certain XRPD peaks for crystalline Form A are summarized in Table 1.
[0239] Table I. X-ray Diffraction Peaks for Form A
[0240]
[0241]
[0242] XRPD data showed peak resolution indicative of crystalline material. The XRPD pattern was successfully indexed, indicating that the sample consisted mainly of a single crystalline phase. Table II shows the space groups consistent with the specified extinction symbol (extinction symbol), as well as unit cell parameter...
Embodiment 3
[0254] Solubility of Form A
[0255] The solubility of the HBr salt of Form A in selected solvents was evaluated by adding solvents under ambient conditions to provide preliminary information for polymorph screening. As shown in Table IV, HBr salts are readily soluble in hexafluoroisopropanol (>128 mg / mL) and dimethylformamide (>114 mg / mL). The material was slightly soluble in methanol, methanol / chloroform (1:1) and methanol / tetrahydrofuran (~14-20 mg / mL). It is estimated to be sparingly soluble in ethanol, 2,2,2-trifluoroethanol, and 1:1 mixtures of tert-butanol / water (~3-7 mg / mL), and in acetone, acetonitrile, chloroform, dichloromethane, acetic acid Ethyl ester, isopropanol, nitromethane, tetrahydrofuran, toluene, water, and dimethylformamide / water mixtures (1:4 and 1:9) showed solubility of less than ~2 mg / mL.
[0256] Table IV
[0257] solvent Solubility (mg / mL) acetone <2
PUM
| Property | Measurement | Unit |
|---|---|---|
| density | aaaaa | aaaaa |
| density | aaaaa | aaaaa |
| density | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More