- 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; 0038; 0041; 0043; 0046; 0048; 0051; 0053;
(2020/08/27)
-
- Preparation method of Eltrombopag key intermediate 3'-amino-2'-hydroxybiphenyl-3-carboxylic acid
-
The invention discloses a preparation method of an Eltrombopag key intermediate 3'-amino-2'-hydroxybiphenyl-3-carboxylic acid. The preparation method comprises the following steps: (1) nitrating o-bromophenol with a nitrating reagent by using water as a s
- -
-
-
- PREPARATION PROCESS OF AN AGONIST OF THE THROMBOPOIETIN RECEPTOR
-
It relates to a preparation process of 2'-(benzyloxy)-3'-nitro-1,1'-biphenyl-3- carboxylic acid or a salt thereof comprising reacting 2-(benzyloxy)-1-bromo- 3-nitrobenzene with a either 3-carboxyphenylboronic acid or a salt thereof or a (C1-C4)-alkyl ester thereof in the presence of Pd(OAc)2, tricydohexylphosphine, a base, an appropriate solvent, and at an appropriate temperature; if appropriate, submitting the compound thus obtained to a hydrolysis reaction; and isolating the compound thus obtained in form of a salt of compound of formula (VI) or in form of the free acid by adding an acid. It also comprises the further preparation to eltrombopag or its salts from the new intermediate thus obtained by subsequent reduction of the nitro group and deprotection of the phenol, conversion of the amine intermediate obtained in a diazonium derivative, and either (1) subsequent reaction with ethyl acetoacetate and with (3,4-dimethylphenyl)hydrazine or a salt thereof, occurring the pyrazole ring formation by intermolecular cyclization, or (2) introduction of the pyrazole ring by reaction with 1-(3,4-dimethylphenyl)-3-methyl-3-pyrazolin-5-one.
- -
-
-
- 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.
- -
-
-
