A kind of preparation method of ticagrelor impurity
A technology of ticagrelor and impurities, which is applied in the field of preparation of ticagrelor impurities, can solve the problems of low content, difficulty in separation, lack of reference substances, etc., and achieve the effect of high yield and simple operation
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0068] The preparation of embodiment 1 ticagrelor impurity
[0069] The ticagrelor impurity is prepared and separated by the following method:
[0070] S1. Dissolve 10.00g of compound I and 21.12g of 1-hydroxybenzotriazole (HOBT) in 50mL of N,N-dimethylformamide (DMF), stir at 4°C for 10min, add 29.96g of 1-ethyl- (3-Dimethylaminopropyl) carbodiimide hydrochloride (EDCI), continue to stir for 10 min, then add 3.28 g of urea and 15 μl of catalyst N-methylmorpholine (NMM), mix and react at 35 ° C for 7 h, After the reaction, add 500mL of ice-brine to cool, let stand for 0.5h, filter, and vacuum-dry at 35°C to obtain 6.43g of compound II, yield 80.63%, purity 96.54%, ESI (m / z) [M+H] + : 154.0478;
[0071] S2. Dissolve 6.43g of compound II and 3.36g of 1-mercaptopropane obtained in step S1 in 30mL of dimethyl sulfoxide, add 11.61g of potassium carbonate in 2 times, add half of each time, mix and react at 45°C for 12h, after the reaction , add 200mL of 0°C ice water to cool, let...
Embodiment 2
[0075] Embodiment 2 different condensing agent compositions, the amount ratio of substance preparation compound II
[0076] Refer to Example 1 for the preparation of ticagrelor impurity, the difference is that in step S1., compound II was prepared using different condensing agent compositions and substance ratios, and refer to Example 1 for other parameters or operations. Calculate and detect the yield and purity of the obtained compound II. See Table 1 for the specific condensing agent composition, material ratio and experimental results.
[0077] Table 1 different condensing agents, the amount of substance than the preparation of compound II
[0078]
[0079]
[0080] It can be seen from Table 1 that the different condensing agent compositions and proportions used in step S1 of the present invention can achieve a yield of more than 70% and a purity of more than 85%. Among them, the combination of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI), 1-hyd...
Embodiment 3
[0081] Example 3 Preparation of Compound III by Different Aprotic Organic Solvents
[0082] Refer to Example 1 for the preparation of ticagrelor impurities, the difference is that in step S2., different aprotic organic solvents were used to prepare Compound III, and other parameters or operations refer to Example 1. Calculate and detect the yield and purity of the obtained compound III. See Table 2 for specific aprotic organic solvents and experimental results.
[0083] Table 2 Preparation of Compound III by Different Aprotic Organic Solvents
[0084] serial number Aprotic organic solvents Yield (%) purity(%) 1 N,N-Dimethylformamide 81.27 98.39 2 Acetonitrile 85.31 97.96 3 Hexamethylphosphonotriamide 79.27 96.12 Example 1 Dimethyl sulfoxide 90.74 98.30
[0085] It can be seen from Table 2 that the aprotic organic solvent used in step S2 of the present invention can achieve a yield of more than 79% and a purity of more than...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More