- Method for synthesizing eltrombopag by using micro-channel reactor
-
The invention discloses a method for synthesizing eltrombopag by using a micro-channel reactor. The method comprises the following steps: S1, material synthesis: adding a raw material 3, 4-dimethylaniline into an acid aqueous solution, dissolving to obtain a material I, dissolving sodium nitrite into water to obtain a material II, dissolving sodium hydrogen sulfite and sodium hydroxide into water to obtain a material III, taking a solution prepared from hydrochloric acid and water as a material IV, adding a raw material 3-amino-2 hydroxyl-[1, 1-biphenyl]-3 formic acid into the acid aqueous solution, dissolving to obtain a material V, and dissolving sodium nitrite into water to obtain a material VI; s2, introducing the material into the micro-channel reactor S3 to obtain a first intermediate 3, 4-dimethylphenylhydrazine hydrochloride, and reacting with ethyl acetoacetate to obtain a second intermediate 2-(3, 4-dimethylphenyl)-5-methyl-1H-pyrazole-3 (2H)-ketone; and S4, introducing the material V and the material VI into the micro-channel reactor for reaction, and enabling the effluent reaction liquid to directly flow into a reaction bottle filled with a 2-(3, 4-dimethylphenyl)-5-methyl-1H-pyrazole-3 (2H)-ketone solution, thereby obtaining eltrombopag.
- -
-
Paragraph 0035; 0071-0085; 0088-0089
(2021/04/14)
-
- Eltrombopag intermediate, preparation method thereof and method for preparing eltrombopag by using intermediate
-
The invention relates to an eltrombopag intermediate, a preparation method thereof and a method for preparing eltrombopag by using the intermediate, which belong to the field of pharmaceutical chemicals. The novel intermediate 2-(2-(3-bromo-2-hydroxy phenyl) hydrazino)-ethyl 3-oxobutyrate of eltrombopag protected by the invention has the advantages of simple structure and low preparation difficulty, and is suitable for preparing eltrombopag; according to the synthetic route of the 4-(2-(3-bromo-2-hydroxy phenyl) hydrazino)-2-(3, 4-dimethyl phenyl)-5-methyl-2, 4-dihydro-3H-pyrazole-3-ketone protected by the invention, the reaction system is simple, the 4-(2-(3-bromo-2-hydroxy phenyl) hydrazino)-2-(3, 4-dimethyl phenyl)-5-methyl-2, 4-dihydro-3H-pyrazole-3-ketone can be directly used for thenext step of reaction without aftertreatment, and is suitable for industrial large-scale production; the total synthesis route of eltrombopag protected by the invention has the advantages of short reaction route, mild reaction conditions, high yield and simple post-treatment, and is suitable for industrial large-scale production.
- -
-
Paragraph 0060-0065
(2021/02/06)
-
- Continuous production process of eltrombopag
-
The invention discloses a continuous production process of eltrombopag. According to the method, a solid reaction container designed in combination with a 3D printing technology is adopted, all the steps in each corresponding reaction chambers are connected in series, raw materials are subjected to nitro reduction, hydrochloric acid acidification and diazotization in sequence and then subjected tocoupling, salifying and refining, and finally, automatic continuous synthesis of eltrombopag is achieved. According to the process, complex manual operation is not needed, chemical synthesis is rapidly carried out, the yield of a synthetic route is improved in a flowing chemical mode, and safety problems caused by manual operation is avoided. The design concept of the invention also reduces the loss of raw materials and solvents, realizes safe, efficient, economical and green continuous synthesis of the drug eltrombopag, and brings a brand-new mode and practical economic benefits to the preparation of the drug.
- -
-
Paragraph 0036; 0039; 0041; 0044; 0046; 0049; 0051; 0054;
(2020/08/27)
-
- Preparation method of eltrombopag
-
The invention relates to the technical field of medicine manufacturing, and discloses a preparation method of eltrombopag. The preparation method comprises the following steps: 1, sequentially carrying out a continuous reaction on a starting material I, glacial acetic acid and hydrobromic acid until the reaction is completed to obtain an intermediate I; 2, reducing the intermediate I by hydrazinehydrate under catalytic action of palladium to obtain an intermediate II; and 3, carrying out diazotization addition on the intermediate II to obtain the eltrombopag. According to the method, nitryl is prevented from being directly reduced by hydrogen on the premise that the medicine quality is guaranteed, so that production can be safely amplified, and market competitiveness of the variety is improved.
- -
-
Paragraph 0020; 0022; 0024; 0027; 0029; 0032
(2019/12/25)
-
- PROCESS FOR PREPARATION OF SUBSTITUTED 3'-HYDROAZINO-DIPHENYL-3-CARBOXYLIC ACID COMPOUNDS
-
The present invention provides a process for the preparation of substituted 3′-hydrazino-biphenyl-3-carboxylic acid compounds. The present invention further provides a process for the preparation of 3′-{N′-[1-(3,4-dimethylphenyl)-3-methyl-5-oxo-1,5-dihydr
- -
-
Paragraph 0220
(2015/03/31)
-
- Thrombopoietin mimetics
-
Invented are non-peptide TPO mimetics. Also invented are novel processes and intermediates used in the preparation of the presently invented compounds. Also invented is a method of treating thrombocytopenia, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a selected hydroxy-1-azobenzene derivative.
- -
-
-