Abstract: The present disclosure provides a preparation method of tofacitinib citrate, which comprises the following steps: passing an intermediate TOF-2 into hydrogen at a normal pressure in the presence of a catalyst to obtain an intermediate TOF-3; in the presence of a solvent and a base, under a reduced pressure of ?490 mmHg to ?760 mmHg, and at a temperature of 10° C. to 25° C., reacting TOF-3 with ethyl cyanoacetate to generate an intermediate TOF-4; heating and dissolving TOF-4 and citric acid in a solvent, and performing separation by cooling to obtain tofacitinib citrate. The present disclosure obtains tofacitinib citrate with high yield, high purity and low impurities by changing a gas flow rate and a reaction temperature and pressure of a hydrogenation reaction. Therefore, the preparation method is suitable for industrial production.

Abstract: The present invention relates to a method for removing water from a compound solution and performing conjugate acid conversion. The method uses a nanometer film to perform reverse osmosis for the compound solution to remove water, and provides a conjugate acid to replace the acidic substances in the compound solution in order to obtain compound conjugate acid salts. The method of the present invention can effectively reduce the water content of the compound solution and replace the conjugate acid of the compound to form the desired compound conjugate acid salt.

Abstract: The present invention relates to a method for purifying polyunsaturated fatty acid using a continuous reactor, and the method comprises: (a) complexing step, (b) cleaning step, (c) extracting step, and (d) concentrating and drying step. The method of the present invention reacts a polyunsaturated fatty acid and a silver salt aqueous solution in a continuous reactor to form a complex of the polyunsaturated fatty acid and silver, and then cleans the complex with a first organic solvent to improve the purity of the complex; afterwards, a second organic solvent is used to extract the purified polyunsaturated fatty acid. The method of the present invention can continuously produce polyunsaturated fatty acids with high yield and high purity.

Abstract: The present invention provides a method for synthesizing etelcalcetide or salts thereof, comprising the steps of: (a) synthesizing the D-amino acids in the formula (I) sequentially by Fmoc solid-phase synthesis, using a solid support as a starting material in solid phase peptide synthesis and sequentially synthesizing a D-form amino acid of formula (I) by Fmoc chemistry; deprotecting Fmoc group and acetylating the amino group to obtain a sequence A comprising protecting groups (PG) in the side chain of D-Cys and D-Arg; (b) removing the protecting group in the side-chain of D-Cys of the sequence A to form a sequence B; (c) disulfide formation at D-Cys of the sequence B by (PG)-L-Cys-OH to obtain a sequence C; (d) using a cleavage solution to remove the protecting groups of the sequence C to give etelcalcetide as formula (I). The present invention can shorten the steps and time for preparing Etelcalcetide.

Abstract: The present invention relates to crystal forms B, C and D of Ribociclib succinate salt and derivatives thereof, and their preparation method and composition. The crystal forms B, C and D of Ribociclib succinate salts are obtained by adding 7-cyclopentyl-N,N-dimethyl-2-(5-(piperain-1-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide solution into succinic acid solution for reaction, stirring the solution under high temperature, filtering the solution after cooling off.

Abstract: The present invention relates a method of preparing a Glucagon-like peptide 2 (GLP-2) analog by gene recombination. The present invention provides an expression vector, which includes: (a) a nucleic acid sequence encoding tag protein; (b) a nucleic acid sequence encoding Smt3 protein (SEQ ID NO: 1); and (c) a nucleic acid sequence encoding linker peptide (SEQ ID NO: 2) and GLP-2 analog. The fusion protein expressed by the expression vector can be cleaved by thrombin, wherein the cleaving position is at the linker peptide, and then the GLP-2 analog is produced.

Abstract: A method for preparing 42-(dimethylphosphinate) Rapamycin (Ridaforolimus) (I) is provided, which has advantages of high conversion rate and no 31,42-bis(dimethyl phosphinate) Rapamycin (III) generated. In the method of the present invention, Rapamycin (II) is firstly reacted with triethyl chlorosilane in a base condition to form 31,42-bis(triethylsilylether) Rapamycin (IV-b), followed by a selective deprotection process to obtain 31-triethylsilylether Rapamycin (V-b). Next, a phosphorylation reaction is performed by using dimethylphosphinic chloride under a base solution to obtain a crude product. Finally, a deprotection reaction is performed in a diluted sulfuric acid solution to obtain a crude product of Ridaforolimus (I). Since the conversion rate of each step of the method of the present invention is higher than 98%, it indicates that the method of the present invention is suitable for industrial production.

Abstract: A method for preparing 42-(dimethylphosphinate) Rapamycin (Ridaforolimus) (I) is provided, which has advantages of high conversion rate and no 31,42-bis(dimethyl phosphinate) Rapamycin (III) generated. In the method of the present invention, Rapamycin (II) is firstly reacted with triethyl chlorosilane in a base condition to form 31,42-bis(triethylsilylether) Rapamycin (IV-b), followed by a selective deprotection process to obtain 31-triethylsilylether Rapamycin (V-b). Next, a phosphorylation reaction is performed by using dimethylphosphinic chloride under a base solution to obtain a crude product. Finally, a deprotection reaction is performed in a diluted sulfuric acid solution to obtain a crude product of Ridaforolimus (I). Since the conversion rate of each step of the method of the present invention is higher than 98%, it indicates that the method of the present invention is suitable for industrial production.

Abstract: A process for making Biolimus A9 comprises reacting sirolimus (or rapamycin) with alkyl benzene sulfonate under the catalyzing of organic base and in the presence of organic solvent to undergo a nucleophilic substitution reaction to obtain the Biolimus A9 with high yield, not only for small-scale laboratory experiment, but also for rendering reproducibility of high yield even after process amplification.

Abstract: A process for making mycophenolate mofetil comprising: conducting a catalytic transesterification by reacting a low-carbon alkyl ester of mycophenolic acid with 2-morpholinoethanol [also named as 4-(2-hydroxyethyl) morpholine] to obtain a crude product of mycophenolate mofetil, which is then isolated and purified.

Abstract: A process for purifying pravastatin sodium comprising the steps of: a. clarifying a fermentation broth containing pravastatin sodium to obtain a clear solution; and adjusting the clear solution to be basic having pH value ranging from pH 10˜13; b. adsorbing the pravastatin sodium with non-ionic resin; eluting the pravastatin sodium by water-soluble organic solvent; and forming a concentrate of pravastatin sodium; c. treating the concentrate with water-soluble anti-solvent or inorganic salt to form a precipitate of pravastatin sodium; and d. recrystallizing the precipitate for making pravastatin sodium crystal with high purity and high yield.