IMPROVED METHOD FOR PREPARING HYDRAZIDES Russian patent published in 2013 - IPC A61K47/48 C07C319/06 C07C319/20 C07C323/52 C07C241/04 C07C243/28 C07C323/48 

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to improved methods for preparing a hydrazide product of hydrazine and acid chlorides, particularly to a method for preparing 3-methyl-3-mercaptobutanoic acid hydrazide. The method involves the stages as follows: (a) preparing a stirred, substantially uniform suspension containing hydrazine and an inert solvent, and (b) continuously adding acid chloride to said suspension, wherein acid chloride has the structure: , wherein P represents a thiol-protective group; each of R₁ and R₂ are specified in a group consisting of C_1-C₅ alkyl; L represents an alkylene linker with continuously adding of the acid chloride solution adjusted so that a reaction temperature maintained within the range of -65°C to -75°C. The invention also refers to a method for preparing a hydrazine suspension involving the stages as follows: (a) cooling the inert solvent to a temperature within the range of -68°C to -75°C; and (b) adding hydrazine drop-by-drop to the specified cold inert solvent; and to a method for preparing an immunoconjugate of calicheamicin member and a monoclonal antibody as a carrier involving preparing monoacylated hydrazide.

EFFECT: method eliminates or limits the formation of the undesired bis-hydrazine side products.

31 cl, 15 ex, 9 tbl