D-17446

Chemical Name: (?-(D,L)-[1,2-Bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II)
项目整合开发状态: Preclinical
项目研究机构: Asta Medica (Originator)
合成路线:The racemic dichloroplatinum(II) complex D-17446 and its meso configurated diastereoisomer were synthesized according to Scheme 1 by reacting K2PtCl4 with (D,L)- and meso-1,2-bis(4-fluorophenyl)ethylenediamine in water at pH 5.5-6.5 at temperatures below 60 C.Complexation with K2PtI4 led to the diiodoplatinum(II) complexes.The corresponding sulfatoplatinum(II) complexes were obtained by addition of Ag2SO4 to the aqueous suspensions of the diiodoplatinum(II) complexes.The diastereoisomeric 1,2-bis(4-fluorophenyl)ethylenediamines were synthesized according to the method described by V鰃tle and Goldschmitt .Meso-1,2-bis(4-fluorophenyl)ethylenediamine was obtained from 4-fluorobenzaldehyde and meso-(2-hydroxyphenyl)ethylenediamine by a stereospecific meso-meso diaza-Cope-rearrangement reaction and subsequent hydrolysis of the product with H2SO4.The racemic compound was synthesized by meso-D,L stereoisomerization of N,N'-bis(4-fluorobenzylidene)-meso-1,2-bis(4-fluorophenyl) ethylenediamine at temperatures below 200 C followed by hydrolysis with H2SO4.Separation of the diastereoisomers was carried out by fractional crystallization of the dihydrosulfates yielding the less water soluble D,L-diamine.