ZENIPLATIN

Originator

Zeniplatin,American Cyanamid (AHP)

Uses

Antineoplastic.

Manufacturing Process

The compound of 2,2-dibromomethyl-1,3-propanediol was prepared by the method M. Saivier (et al.), Can. J. Chem; 44, 1599 (1966).
A mixture of 13.1 g of 2,2-dibromomethyl-1,3-propanediol, 6.5 g of sodium azide and 750 ml of dimethylformamide was stirred and heated at 110°- 120°C for 20 h, then clarified and the filtrate evaporated. The residue was extracted three times with dichloromethane. The extracts were combined and evaporated, giving 13.65 g of 2,2-bis(azidomethyl)-1,3-propanediol, compound with dimethylformamide.
A 13.0 g portion of the 2,2-bis(azidomethyl)-1,3-propanediol was reduced with 0.1 g of platinum dioxide in ethanol, using 50 lb of hydrogen pressure for 20 h. The mixture was then filtered and the filtrate concentrated to dryness, giving 9.34 g of 2,2-bis(aminomethyl)-1,3-propanediol as a pale yellow oil.
A mixture of 1.34 g of 2,2-bis(aminomethyl)-1,3-propanediol, 4.15 g of potassium dichloroplatinate and 22 ml of water was stirred for 2 h, then cooled, the solid collected and washed three times with cold water. This solid was recrystallized from 60 ml of hot water, giving 890.0 mg of the desired [2,2-bis(aminomethyl)-1,3-propanediol-N,N']dichloroplatinum as beige crystals, melting point 223°-225°C (dec.).
A mixture of 0.8 g of [2,2-bis(aminomethyl)-1,3-propanediol- N,N']dichloroplatinum and 0.78 g of the disilver salt of 1,1-cyclobutane dicarboxylic acid in 50 ml of water was stirred in the dark overnight and then filtered. The filtrate was evaporated to dryness, giving 0.72 g of the desired [2,2-bis(aminomethyl)-1,3-propanediol-N,N'][[1,1'- cyclobutanedicarboxylato](2-)-O1,O1]platinum as a beige powder, melting point 202°-205°C (dec.).

Therapeutic Function

Antineoplastic