545445-44-1Relevant articles and documents
Preparation method of apixaban intermediate suitable for industrial production
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, (2021/08/19)
The invention discloses a synthesis method of an apixaban intermediate suitable for industrial production. The method comprises the following steps: carrying out phase-transfer catalytic amidation reaction on paranitroaniline and 5-chlorovaleryl chloride in an organic phase and water phase two-phase system under an inorganic weakly alkaline condition to obtain an APM01 solution, and adding a sodium hydroxide water solution, and cyclizing in a pot to obtain an APM02 solution; directly carrying out alpha-reactive hydrogen dichlorination on an APM02 organic solution and phosphorus pentachloride after simple acid pickling, liquid separation and drying to obtain an APM03 solution; carrying out condensation-elimination reaction on the APM03 solution and excessive morpholine after simple acid pickling and liquid separation, and carrying out simple crystallization and purification treatment to separate out an APM04 solid, and reducing the APM04 into APM05 by sodium sulfide; and carrying out amidation-cyclization two-step one-pot reaction on the APM05 and 5-chlorovaleryl chloride to prepare a key intermediate APM07. According to the method, the synthesis efficiency of the apixaban intermediate is improved, the reaction is mild, and dangerous NaH and other expensive reagents are not used, so that the production cost is saved, the operation is simple, and the method is suitable for industrial popularization.
Apixaban intermediate and preparation method thereof
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, (2020/05/01)
The embodiment of the invention discloses an apixaban intermediate and a preparation method thereof. The preparation method comprises the following steps: preparation of an intermediate 2, preparationof an intermediate 3, preparation of an intermediate 4, preparation of an intermediate 5, and preparation of apixaban key intermediate 5, 6-dihydro-3-(4-morpholinyl)-1-[4-(2-oxo-1-piperidyl) phenyl]-2 (1H)-pyridone. According to the apixaban intermediate 5, 6-dihydro-3-(4-morpholinyl)-1-[4-(2-oxo-1-piperidyl) phenyl]-2 (1H)-pyridone and the preparation method thereof provided by the invention, the operation is simple, the reaction condition is mild, the requirement on equipment is low, scale-up production is easier, the yield is high, and the purity of the product is greater than 99%.
Preparation method of 5,6-dihydropyridine-2 (1H)-one derivative
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, (2020/06/17)
The invention provides a preparation method of a 5,6-dihydropyridine-2 (1H)-one derivative, and particularly relates to a 1-(piperidine-2-keto-1-yl)-4-(5,6-dihydro-3-R substituent pyridine-2 (1H)-keto-1-yl) benzene preparation method, wherein the R substituent is chlorine or morpholine-4-yl. According to the invention, p-acetamido aniline is used as a raw material, and amidation with delta-valerolactone, halogenation with a halogenation reagent or sulfonylation with sulfonyl chloride, condensation, deacetylation, amidation with 2,2-dichloro-delta-valerolactone, halogenation with a halogenationreagent or sulfonylation with sulfonyl chloride, condensation elimination or condensation elimination substitution in the presence of morpholine are performed to obtain the target product. Accordingto the invention, the raw materials used in the preparation method are cheap, easy to obtain and low in cost; the process operation is simple, reaction conditions are easy to realize, the wastewater yield is low, and safety and greenness are realized; and the reaction selectivity of each step is high, the product yield and purity are high, and industrial production is facilitated.