- Preparation method of amifostine trihydrate
-
The invention discloses a novel preparation method of amifostine trihydrate. According to the method, thiophosphoryl chloride is directly used as a reaction raw material to react with N-(2-bromoethyl)-1, 3-propane diamine dihydrobromide in the presence of alkali and a phase transfer catalyst by using a sulfolane/water solvent system to prepare the amifostine trihydrate. Compared with the prior art, the method has the advantages that the process flow is shortened, and the raw material conversion rate, the reaction efficiency and the yield and purity of the target product are improved.
- -
-
Paragraph 0023-0035
(2021/05/05)
-
- Synthetic method of amifostine
-
The invention discloses a synthetic method of amifostine. The method includes the following steps that 1, a compound shown in the formula (IV) reacts with hydrogen in the presence of rhodium oxide, gold oxide and raney nickel to obtain a compound shown in formula (III); 2, the compound shown in formula (III) reacts with hydrogen bromide in a mixed solvent formed by water and C1-5 alcohol solventsto obtain a compound shown in the formula (II) at 0-20 DEG C; 3, the compound shown in formula (II) reacts with sodium thiophosphate to obtain amifostine shown in the formula (I). Through the method,high-yield and high-purity products can be obtained, the process is simple, and the method is suitable for industrial production.
- -
-
Paragraph 0031-0032; 0035-0036; 0039-0040; 0043
(2019/07/10)
-
- A three-hydrated 3 - amino propyl amine ethyl phosphorothioic acid preparation method
-
The invention discloses a preparation method for trihydrate 3-amino propyl aminoethyl thiophosphoric acid. The preparation comprises the following steps of reacting N-(2-bromoethyl)-1,3-propane diamine and sodium thiophosphate in water and an organic solvent. The organic solvent is one or more selected from ethanol, methanol, isopropanol, acetic acid, acetone, acetonitrile and tetrahydrofuran. The preparation method provided by the invention is mild in conditions, takes use of the most common organic solvent, is fast in reaction speed, is safe and reliable, and is convenient for operations and relatively low in cost. Besides, residual solvent can be removed and detected easily; the purity of the obtained crude product is relatively high (98%); and the preparation method is suitable for industrial production. A reaction equation is shown in the description.
- -
-
Paragraph 0029-0045; 0046; 0047; 0048-0053
(2017/04/20)
-
- A thiophosphate synthetic method of compound and the method in a plurality of pharmaceutical application in the synthesis of (by machine translation)
-
The invention discloses a having the general formula (III) of the thiophosphate synthetic method of compound, the purpose is to provide a novel, condition is simple, easy to industrial production of the thiophosphate synthetic method of compound. The method is to have the general formula (I) of the organophosphorus oxygen apperception compound having the general formula (II) with a mercaptan or phenyl-sulfhydryl apperception compound mixed, under the effects of catalyst, obtained by the reaction of the formula (III) of the thiophosphate compound. The method of the invention, can be cheap efficient synthesis of thiophosphate compounds, in actual production will have extensive application prospect. (by machine translation)
- -
-
Paragraph 0255; 0256; 0257; 0258
(2017/07/20)
-
- A process for the preparation of green amifostin
-
The invention relates to the field of drug synthesis, and discloses an environment-friendly technology for preparing medicinal amifostine. The technology is as follows: mixing a N-bromoethyl-1,3-propanediamine dihydrobromide solution with sodium thiophosphate at the concentration of a aqueous solution of 10-70%, keeping mol ratio within the range of 1.0:0.8-1.2, and reaction temperature at 5.0-60 DEG C, using a lower alcohol or a polyhydric alcohol as an accelerant to generate the amifostine product, directly filtering the product to obtain the crude product of amifostine, and carrying out recrystallization and purification to the crude product to obtain medicinal amifostine trihydrate, wherein the amifostine content is larger than or equal to 99.5%, the content of sodium thiophosphate is smaller than 0.1%, the content of other related single substances is smaller than 0.1%, and the content of the whole related substances is lower than 0.3%. The preparation method is free from high boiling point aprotic solvent residual; the medicinal safety is improved; the filtrated stock can be recovered by distilling at normal pressure; the accelerant can be recycled. Amifostine prepared by the method is high in the quality, free from high boiling point aprotic solvent residual, environment-friendly, efficient, easy to operate, low in cost, and suitable for industrial scale production.
- -
-
Paragraph 0023-0026
(2017/02/24)
-
- A method of preparing pharmaceutical amifostin
-
The invention relates to the field of drug synthesis and discloses a method for preparing medicinal amifostine trihydrate with high efficiency and convenience. The method comprises the following steps: under the conditions that the aqueous solution concentration is 10-70%, the molecular molar ratio is in the range of 1.0 : (0.8-1.2) and the reaction temperature is in the range of 5.0-60 DEG C, reacting a N-bromoethyl-1,3-propanediamine dihydrobromide solution and a sodium thiosulfate solution in the presence of N,N-dimethylacetamide (DMAC) as a promoter to produce amifostine; filtering the reaction liquid without any treatment to obtain crude amifostine; purifying through recrystallization using a compound solvent to obtain medicinal amifostine with a content of higher than or equal to 99.7%, a thiol content of lower than 0.2%, a sodium thiosulfate content of lower than 0.1%, an other single relevant substance content of lower than 0.1% and a total impurity content of lower than 0.3%. The method is environment-friendly, highly-efficient, low in cost, convenient in operation and suitable for industrial large-scale production.
- -
-
Paragraph 0019-0021
(2017/03/17)
-
- Crystalline amifostine compositions and methods of the preparation and use of same
-
The present invention relates to a sterile, stable vacuum dried crystalline amifostine composition and, optionally, pharmaceutically acceptable excipient(s). Typically, the crystalline compositions of the present invention exhibit enhanced stability at temperatures ranging from about 4° C. to about ambient temperature for a period of at least 2 years relative to existing solid vacuum dried amorphous amifostine preparations. The reconstituted compositions of the present invention are suitable for administration to humans as a radio- or chemoprotecting agent.
- -
-
-
- CHIMIE DES RADIOPROTECTEURS: REVISION DE LA SYNTHESE DES ACIDES S- ET S-PHOSPHOROTHIOIQUES
-
Simple, reproducible and detailed preparations of S- and S- phosphorothioic acids (HO)2P(O)-S-(CH2)2-NH-(CH2)3-NH-R (R=H and CH3), named WR 2721 and WR 1680 respectively, are described.The yields of each step have been optimized to facilitate the synthesis of these compounds of large interest in the cancer radio- and chemotherapy.
- Laduranty, Joelle,Lion, Claude,Mesnard, Daniele,Miginiac, Leone
-
p. 903 - 912
(2007/10/02)
-