Patent ID: 6518428
Filing Date: 2003-02-11
Classification: A61K,A61P,C07F

Abstract:
A method to prepare a cisplatinum complex of the formula Ia or Ib comprising the steps of:a) reacting [PtA4]2 or a salt thereof with L in a first aprotic solvent at a temperature of 30Â° C. to 100Â° C. to form [PtA3(L)]âˆ’, with the proviso that when the first solvent is DMF, the temperature is below 60Â° C.; b) without evaporating the first solvent, reacting the [PtA3(L)]âˆ’ with Lâ€² in a second solvent to form cis-[PtA2(Lâ€²)(L)]; c) when the cisplatinum complex is of the formula Ib and Y is hydroxy or a halogen, reacting the cis-[PtA2(Lâ€²)(L)] formed in step b) with H2O2 when Y is hydroxy, or a halogen when Y is a halogen, to form c,t,c-[PtA2Y2(Lâ€²)(L)]; and d) when the cisplatinum complex is of the formula Ib and Y is carboxylate, carbamate or carbonate ester, first forming [PtA2OH2(Lâ€²)(L)] from [PtA2(Lâ€²)(L)] by reacting the cis-[PtA2(Lâ€²)(L)] formed in step b) with H2O2, and then reacting the [PtA2OH2(Lâ€²)(L)] with an acylating agent to form [PtA2Y2(Lâ€²)(L)]; wherein L and Lâ€² are different and are each an amine or a substituted amine, wherein said substituted amine is substituted with at least one straight, branched or cyclic aliphatic, aryl, nonaromatic or aromatic heterocyclic group, with the proviso that only Lâ€² can be NH3 and that at least one of L and Lâ€² is a substituted cyclic amine; wherein A may be the same or different and is a halide or a leaving group; and wherein Y is halogen, hydroxy, carboxylate, carbamate or carbonate ester.