Patent ID: 8546549
Filing Date: 2013-10-01
Classification: A61P,C07C,C07D,C07H

Abstract:
1. A method of preparing compounds of the following formula: wherein Z is selected from the group consisting of and wherein W′ is comprising the steps of: a. reacting a carboxylic acid of the formula with a mercapto compound of the formula in an alcohol solvent in the presence of an alkyl carboxylic acid, alk b. isolating the bilinker-carboxylic acid of step (a); c. reacting the isolated bilinker-carboxylic acid of step (b) with N-hydroxysuccinimide, 2,3,5,6-tetrafluorophenol, pentafluorophenol, 4-nitrophenol, 2,4-dinitrophenol, or N-hydroxysulfosuccinimide in the presence of 1,3-dicyclohexylcarbodiimide (DCC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), or N,N′-disuccinimdyl carbonate in an inert solvent containing 0-50% N,N-dimethylformamide (DMF) to generate a trilinker-activated ester of the formula: d. reacting the trilinker-activated ester formed in step c in the presence of a base or an organic base with a methyltrithio antitumor antibiotic CH e. isolating the activated ester of step (d) and purifying to yield antitumor antibiotics of the formula: