Patent classifications
C07C65/105
PROCESS FOR THE PREPARATION OF KEY INTERMEDIATES FOR THE SYNTHESIS OF ELTROMBOPAG OR SALT THEREOF
Object of the present invention is an improved process for the preparation of key intermediates for the synthesis of Eltrombopag, passing through/using intermediate 5′-Chloro-2′-hydroxy[1,1′-biphenyl]-3-carboxylic acid alkaline metal salt of formula: wherein A is an alkaline metal.
##STR00001##
PROCESS FOR THE PREPARATION OF KEY INTERMEDIATES FOR THE SYNTHESIS OF ELTROMBOPAG OR SALT THEREOF
Object of the present invention is an improved process for the preparation of key intermediates for the synthesis of Eltrombopag, passing through/using intermediate 5′-Chloro-2′-hydroxy[1,1′-biphenyl]-3-carboxylic acid alkaline metal salt of formula: wherein A is an alkaline metal.
##STR00001##
METHOD FOR PREPARING 4,4'-DIHYDROXY-[1,1'-BIPHENYL-3,3'-DICARBOXYLIC ACID]
The present invention relates to a method for preparing 4,4′-dihydroxy-[1,1′-biphenyl-3,3′-dicarboxylic acid], the method comprising a step for preparing a compound represented by chemical formula 1 by reacting a compound represented by chemical formula 2 with a base according to reaction formula 1. [reaction formula 1] [chemical formula 1] [chemical formula 2] According to the present invention, because use of additional carbon dioxide is unnecessary during the reaction, internal pressure is lowered during same, the reaction can be carried out at a lower temperature, the yield from the synthesis is notably improved as hardening of the resulting substance is absent, and H.sub.4dobpdc can be synthesized in large amounts as an additional process for obtaining pure ligands is unnecessary.
METHOD FOR PREPARING 4,4'-DIHYDROXY-[1,1'-BIPHENYL-3,3'-DICARBOXYLIC ACID]
The present invention relates to a method for preparing 4,4′-dihydroxy-[1,1′-biphenyl-3,3′-dicarboxylic acid], the method comprising a step for preparing a compound represented by chemical formula 1 by reacting a compound represented by chemical formula 2 with a base according to reaction formula 1. [reaction formula 1] [chemical formula 1] [chemical formula 2] According to the present invention, because use of additional carbon dioxide is unnecessary during the reaction, internal pressure is lowered during same, the reaction can be carried out at a lower temperature, the yield from the synthesis is notably improved as hardening of the resulting substance is absent, and H.sub.4dobpdc can be synthesized in large amounts as an additional process for obtaining pure ligands is unnecessary.
Preparation and purification of biphenyldicarboxylic acids
Processes are described for purifying a biphenyldicarboxylic acid product containing one or more impurities, particularly at least formylbiphenylcarboxylic acid. In the processes, a mixture comprising the biphenyldicarboxylic acid product is contacted with hydrogen in the presence of a hydrogenation catalyst under conditions to selectively reduce at least part of the formylbiphenylcarboxylic acid to produce a hydrogenation effluent comprising (i) hydroxymethylbiphenylcarboxylic acid and/or methylbiphenylcarboxylic acid, and (ii) biphenylcarboxylic acid. At least a portion of the biphenyldicarboxylic acid is then separated from the hydrogenation effluent. Advantageously, a polyester product may be produced from the separated biphenyldicarboxylic acid.
Preparation and purification of biphenyldicarboxylic acids
Processes are described for purifying a biphenyldicarboxylic acid product containing one or more impurities, particularly at least formylbiphenylcarboxylic acid. In the processes, a mixture comprising the biphenyldicarboxylic acid product is contacted with hydrogen in the presence of a hydrogenation catalyst under conditions to selectively reduce at least part of the formylbiphenylcarboxylic acid to produce a hydrogenation effluent comprising (i) hydroxymethylbiphenylcarboxylic acid and/or methylbiphenylcarboxylic acid, and (ii) biphenylcarboxylic acid. At least a portion of the biphenyldicarboxylic acid is then separated from the hydrogenation effluent. Advantageously, a polyester product may be produced from the separated biphenyldicarboxylic acid.
COMPOUNDS, COMPOSITIONS, METHODS OF USING, AND METHODS FOR PREPARING COMPOUNDS
In some embodiments of the invention, inventive compounds (e.g., Formula (I), (IA), (II), and (III), and urolithin derivatives) are disclosed. Other embodiments include compositions (e.g., pharmaceutical compositions) comprising the inventive compound. Still other embodiments of the invention include compositions (e.g., pharmaceutical compositions) for treating, for example, certain diseases using the inventive compounds. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases). Further embodiments include methods for making the inventive compounds. Additional embodiments of the invention are also discussed herein.
METAL ORGANIC FRAMEWORKS (MOFs) AND METHODS OF SYNTHESIZING AND USING THE SAME
A new metal organic framework (MOF) series and method of synthesizing the same are disclosed which includes an organic linking ligand having the formula:
##STR00001##
and a metal ion bonded to the organic linking ligand.
APPLYING HANSEN SOLUBILITY PARAMETERS TO METAL-ORGANIC FRAMEWORK SYNTHESIS CONDITIONS
A method suitable for use in investigating synthesis conditions for metal-organic frameworks may include: identifying synthesis conditions that includes a first solvent system by which a metal-organic framework is successfully synthesized; and synthesizing the metal-organic framework under substantially the same synthesis conditions but with a second solvent system (or a comparable solvent system) having a difference (R.sub.a) between Hansen solubility parameters of 5 MPa.sup.0.5 or less as compared to the first solvent system.
APPLYING HANSEN SOLUBILITY PARAMETERS TO METAL-ORGANIC FRAMEWORK SYNTHESIS CONDITIONS
A method suitable for use in investigating synthesis conditions for metal-organic frameworks may include: identifying synthesis conditions that includes a first solvent system by which a metal-organic framework is successfully synthesized; and synthesizing the metal-organic framework under substantially the same synthesis conditions but with a second solvent system (or a comparable solvent system) having a difference (R.sub.a) between Hansen solubility parameters of 5 MPa.sup.0.5 or less as compared to the first solvent system.