The present invention relates to a process for the preparation of the mono sodium salt of the derivative 3,5-diiodo-O-[3-iodo-4-(sulphooxy)phenyl]-L-tyrosine (T3S) by starting from the corresponding phenolic compound, in the presence of chlorosulfonic acid and dimethylacetamide as a solvent. The so obtained T3S compound may conveniently be isolated in a pure form as a solid in good yields. The present invention further relates to the process for T3S preparation, wherein the starting reagent is T2 and further comprising the formulation of such compound in tablets. Furthermore, the invention discloses non-radioactive immunoassays based on T3S derivatives.

The present invention relates to a process for the preparation of the mono sodium salt of the derivative 3,5-diiodo-O-[3-iodo-4-(sulphooxy)phenyl]-L-tyrosine (T3S) by starting from the corresponding phenolic compound, in the presence of chlorosulfonic acid and dimethylacetamide as a solvent. The so obtained T3S compound may conveniently be isolated in a pure form as a solid in good yields. The present invention further relates to the process for T3S preparation, wherein the starting reagent is T2 and further comprising the formulation of such compound in tablets. Furthermore, the invention discloses non-radioactive immunoassays based on T3S derivatives.

Provided is an improved process for the preparation N-[4-[[4-(diethyl amino) phenyl](2,5-disulfophenyl)methylene]-2,5-cyclohexadien-1-ylidene]-N-ethylethanaminium inner salt sodium salt (Isosulfan blue) of formula I. It also relates to highly pure novel crystalline form of Isosulfan blue hydrate and its process for the preparation thereof. It also relates to an improved process for the preparation of Isosulfan blue sodium hydrate having not more than 0.2% of desethyl impurity of formula A.

##STR00001##

Provided is an improved process for the preparation N-[4-[[4-(diethyl amino) phenyl](2,5-disulfophenyl)methylene]-2,5-cyclohexadien-1-ylidene]-N-ethylethanaminium inner salt sodium salt (Isosulfan blue) of formula I. It also relates to highly pure novel crystalline form of Isosulfan blue hydrate and its process for the preparation thereof. It also relates to an improved process for the preparation of Isosulfan blue sodium hydrate having not more than 0.2% of desethyl impurity of formula A.

##STR00001##

[Problem]

To provide an industrially preferred method for producing a sulfoxide derivative.

[Solution]

A method for producing a sulfoxide derivative represented by general formula (1),

##STR00001##

the method being characterized in that a sulfide derivative represented by general formula (2)

##STR00002##

is reacted with an oxidizing agent in the presence of a catalyst that is a metal-ligand complex containing a metal compound and, as a ligand, a compound represented by general formula (3),

##STR00003##

and in the presence of a benzoic acid compound represented by general formula (4).

##STR00004##

The invention relates to a method for producing organometallic compounds RMn (M=alkali or alkaline earth element, R=alkyl residue) where n=valence of the metal M and R=alkyl residue with 2 to 18 C atoms, in which method an olefin is hydrometalated in an alkyl methyl ether, or in a solvent mixture containing an alkyl methyl ether, by means of the metal M and in the presence of a hydrogen source and in the presence of a transition metal catalyst, wherein the molar ratio between alkyl methyl ether and metal M is at least 0.01:1 and at most 50:1.

The invention relates to a method for producing organometallic compounds RMn (M=alkali or alkaline earth element, R=alkyl residue) where n=valence of the metal M and R=alkyl residue with 2 to 18 C atoms, in which method an olefin is hydrometalated in an alkyl methyl ether, or in a solvent mixture containing an alkyl methyl ether, by means of the metal M and in the presence of a hydrogen source and in the presence of a transition metal catalyst, wherein the molar ratio between alkyl methyl ether and metal M is at least 0.01:1 and at most 50:1.

The present invention relates to a process for providing a compound of formula (I): ##STR00001##
wherein R is hydrogen or R, wherein R is (C.sub.1-C.sub.4)alkyl, and Hal is a halogen, the process comprising the step of:
reacting a compound of formula (II) ##STR00002##
wherein Hal is defined as above,
with an alkali metal alkoxide of the formula XOR, wherein X is an alkali metal, and R is defined as above.

The present invention relates to a process for providing a compound of formula (I): ##STR00001##
wherein R is hydrogen or R, wherein R is (C.sub.1-C.sub.4)alkyl, and Hal is a halogen, the process comprising the step of:
reacting a compound of formula (II) ##STR00002##
wherein Hal is defined as above,
with an alkali metal alkoxide of the formula XOR, wherein X is an alkali metal, and R is defined as above.

Salicylic acid-based polymeric CEST contrast agents targeting prostate-specific membrane antigen, pharmaceutical composition comprising the same and methods of use thereof are disclosed.