4 results about "Sofosbuvir" patented technology

The application discloses a method for determining the concentration of sofosbuvir in blood plasma and screening a non-isotope labeled internal standard, wherein anlotinib, imatinib, olaparib, osimertinib and pralsetinib are used as internal standards, quantitative analysis is performed by combining LC-MS / MS with protein precipitation pretreatment. The internal standard screening method is screened from candidate compounds by systematically evaluating four dimensions of protein precipitation compatibility, matrix effect, detection stability and extraction recovery, and an internal standard consistent with the behavior of the measured substance is screened. The application solves the problem of the lack of commercial isotope internal standards for sofosbuvir, and provides a reliable and efficient detection and internal standard screening scheme.

The invention provides a fluorination preparation process of a sofosbuvir intermediate, and relates to the technical field of pharmaceutical chemicals. The preparation process comprises the following steps: (1) dissolving a compound A in a first solvent, and then adding alkali and paratoluensulfonyl chloride to carry out affinity substitution reaction; after the reaction is finished, contacting the reaction liquid with water, and separating an organic phase; drying and concentrating to obtain a crude intermediate product; (2) carrying out fluorination reaction on the crude intermediate product and a fluorinating agent under the action of a Lewis acid catalyst; after the reaction is finished, contacting the reaction liquid with water, and separating an organic phase; then extracting and recrystallizing to obtain a target compound B; wherein the structural formula of the compound A is as shown in a formula I, and the structural formula of the compound B is as shown in a formula II. According to the fluorination preparation process of the sofosbuvir intermediate, the compound B can be efficiently obtained, the process is greatly simplified, the production cost is saved, and the fluorination preparation process has important industrial application value.

The invention relates to a sofosbuvir preparation method, which comprises: placing a compound represented by a formula I, a compound represented by a formula II and 2, 6-dimethyl pyridine in THF, mixing at a normal temperature, slowly adding a dimethyl aluminum chloride solution, carrying out a reaction at a normal temperature for 5-10 h, and carrying out a quenching reaction with a 10-30% acid solution to obtain the sofosbuvir. The method provided by the invention does not need alternate operation of heating and cooling, obviously shortens the reaction period, and has the advantages of low catalyst dosage, high product yield, good reaction selectivity, low impurity yield, more suitability for industrial production and the like.

The invention relates to the technical field of medicinal chemistry, in particular to an asymmetric catalytic synthesis method of a phosphorus chiral nucleoside derivative sofosbuvir. The method comprises the following steps: sequentially adding a nucleoside compound (II), a chiral organic catalyst, a 4molecular sieve, an organic solvent and organic alkali into a reaction container in an inert gas atmosphere under anhydrous and anaerobic conditions, and stirring and activating at-30 DEG C to 0 DEG C; then dropwise adding P-racemic chlorophosphate (I), and continuing to react for 12-36 hours at the same temperature; after the reaction is finished, adding water to quench unreacted (I), and carrying out post-treatment to obtain a sofosbuvir product; wherein the chiral organic catalyst is a bicyclic imidazole catalyst C1-C6. The Sp configuration product sofosbuvir with high diastereomer purity is obtained through the method, and the method has the advantages of being easy and convenient to operate, mild in condition, environmentally friendly, capable of amplifying the process and the like and is suitable for green and efficient synthesis of antiviral drugs.