Method for preparing ticagrelor and intermediate of ticagrelor
A technology for ticagrelor and a compound is applied in the field of preparing ticagrelor and its intermediates, and can solve the problems of being difficult to cure, affecting the quality of ticagrelor products, and the like
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Embodiment 1
[0072] Example 1 compound 2-b’ synthesis
[0073]
[0074] In a 250ml single-necked round bottom flask, add 160ml of ethanol, 60ml (0.70mol) of 36%-38% concentrated hydrochloric acid, compound 2-a’ 20g (0.05mol), stirred overnight at room temperature. Compounds detected by TLC 2-a’ After the reaction is complete, post-treatment is carried out. 40% sodium hydroxide aqueous solution was added dropwise under ice-cooling to neutralize the reaction solution to Ph=6-7. After the ethanol was distilled off under reduced pressure, 200 ml of ethyl acetate was added to extract the aqueous phase three times. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the ethyl acetate solvent was distilled off under reduced pressure to obtain 2-b’ The product was 14 g of light yellow oily matter, the yield was 77.8%, and the HPLC purity was greater than 98%. 1 H NMR (400M, CDCl 3 ) δ: 7.30-7.34 (m, 5H), 5.4 (s, 2H), 4.22 (s, 2H), 4.12 (...
Embodiment 2
[0075] Example 2 compound 2-c’ synthesis
[0076]
[0077] compound 2-b’ 4g (11.3mmol) and 5.5g (68.9mmol) of pyridine were dissolved in 20ml of dichloromethane, and the temperature was lowered to -80°C under the protection of nitrogen. Dissolve 2g (6.7mmol) of bis(trichloromethyl)carbonate in 20ml of dichloromethane, and slowly add it dropwise to the above reaction solution. The temperature of the dropwise addition process was controlled at -80°C. After the dropwise addition, continue to stir for 30 minutes, then slowly warm up to room temperature and continue to stir for 30-60 minutes. Compounds detected by TLC 2-b’ After the reaction is complete, post-treatment is carried out. The reaction was terminated by adding a saturated ammonium chloride aqueous solution dropwise until no bubbles were generated in the reaction solution. Separate the layers, and wash the organic phase with 1mol / L hydrochloric acid. Separate the liquid, and wash the organic phase with water. ...
Embodiment 3
[0078] Example 3 Compound 2-d’ synthesis
[0079]
[0080] Add 1.32ml (2.64mmol) of 2mol / L LiBH4 solution in THF to a 100ml three-neck round bottom flask, and cool down to -10°C. Under nitrogen protection, the compound 2-c’ 1g (2.64mmol) was dissolved in 5ml THF, and slowly added dropwise to the above solution. Stirring was continued for 2 hours after the dropwise addition was complete. Compounds detected by TLC 2-c After the reaction is complete, post-treatment is carried out. The reaction solution was poured into ice water, stirred for 15 minutes, and 10 ml of ethyl acetate was added to extract the aqueous phase twice. The ethyl acetate phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated under reduced pressure to obtain the compound 2-d’ The crude product was 0.8g, and the compound was obtained after separation by column chromatography (silica gel column, eluent petroleum ether: ethyl acetate = 3:2) 2-d’ The product ...
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