Process for the preparation of 1,2-diaminocyclohexane-platinum(II) complexes
View Patent ↗A process for the preparation of diaminocyclohexane-platinum(II)-dicarboxylates has the following steps: B Conversion of K 2 PtX 2 with 1,2-diaminocyclohexane (DACH) to (2): C Conversion of (2) with too little quantity of silver salt Ag n A to (3): and removal of the resulting AgX precipitate. D Conversion of (3) with a dicarboxylate to (1): F Isolation of the product (1), wherein R 1 and R 2 together form a dicarboxylato group, X stands for Cl or I, A for a 1-2-valent anion of a mineral acid, and n stands for 1 or 2.
1. A process for the preparation of diaminocyclohexane-platinum(II)-dicarboxylates comprising the following steps:
B) Converting K 2 PtX 4 with 1,2-diaminocyclohexane (DACH) to (2):
C) Converting (2) with a silver salt Ag n A to (3):
and removal of the resulting AgX precipitate;
D) Converting (3) with ammonium oxalate to (1):
F) Isolating the product (1),
wherein R 1 and R 2 together form a dicarboxylato group, X stands for CI or I, A stands for a 1-2-valent anion of a mineral acid, and n stands for 1 or 2, and wherein in step C an understochiometric amount of silver salt is used.
2. Process in accordance with claim 1 , wherein X is I.
3. Process in accordance with claim 2 , which is for the preparation of oxalipiatinum, and further comprises the following preceding step:
A) Converting K 2 PtCl 4 with Kl to K 2 Ptl 4 .
4. Process in accordance with claim 1 , wherein in step C the mixture is cooled to 1-10 degrees C. before the removal of the precipitate.
5. Process in accordance with claim 1 , wherein the solution derived after step D
E) is purified twice and filtered with activated carbon.
6. Process in accordance with claim 1 , wherein the solution derived after step D or E is concentrated to less than 10 ml/g product.
7. Process in accordance with claim 1 , which is conducted in purified endotoxin-free water with limited bacterial content (“purified water” according to European Pharmacopoeia, 4 th Edition, and/or U.S. Pharmacopoeia, 27 th Edition).
8. Process in accordance with claim 7 , whereby the water is “highly purified water” according to EP (European Pharmacopoeia, 4 th edition, 2002).
9. Process in accordance with claim 5 , wherein the solution derived after step E) is sterilely filtered and then concentrated and
F) the solid content is filtered and dried.
10. Process in accordance with claim 1 , wherein after step (F)
G) the product is washed with “purified water” according to European Pharmacopoeia, 4 th Edition, and/or U.S. Pharmacopoeia, 27 th Edition; or “highly purified water” according to European Pharmacopoeia, 4 th Edition; and subsequently washed with a light boiling solvent that is pharmacologically acceptable.
11. Process in accordance with claim 10 , wherein the solvent is acetone or methanol.