Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-01-31
1998-05-12
Nazario-Gonzalez, Porfirio
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
556137, 514492, C07D20500, C07F 1500
Patent
active
057507163
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCES TO RELATED APPLICATIONS
This application was filed as a request for U.S. examination under 35 U.S.C. .sctn. 371 of International application No. PCT/JP96/01142 filed Apr. 25, 1996.
TECHNICAL FIELD
The present invention relates to a method of producing the following platinum compound used as an anticancer drug. ##STR2##
BACKGROUND ART
Methods of producing and purifying platinum compound (A) having anticancer activity are disclosed in the specification W091009041. Namely, the production methods represented by the following formulae are disclosed. ##STR3##
However, the above production method (I) has the problem that, although compound (D) used is produced by ion exchange of compound (F) using a strong anion-exchange resin, the strong anion-exchange resin is expensive and requires preparation for 3 to 5 days. The production method (II) has the problem that the two steps are required for obtaining compound (A). The methods disclosed in the specification WO91009041 have a yield of 60 to 65%.
An object of the present invention is to solve the above problems and provide a method which is capable of producing and purifying a platinum complex represented by formula (A) with high purity.
DISCLOSURE OF THE INVENTION
The present invention relates to a method of producing a platinum (II) complex represented by the following formula (A) comprising: ##STR4##
reacting a dichloroplatinum complex represented by the following formula (B), ##STR5## and a tetronic acid derivative represented by the following formula (C) in coexistence with a silver salt and a barium salt. ##STR6## The present invention also relates to a method of improving the purity of optically active amines comprising mixing 1-trans-1,2-diaminocylcohexane or d-trans-1,2-diaminocylcohexane and an acid having no optically active point, and recrystallizing the resultant salt from a water-soluble organic solvent or a mixed solvent of water and a water-soluble organic solvent.
BEST MODE FOR CARRYING OUT THE INVENTION
The present invention is described with reference to preferred embodiments. It was found that a platinum complex represented by formula (A) can be produced by a one-step reaction in which equivalents or less of silver sulfate and barium hydroxide are reacted in water or a mixed solvent of water and an alcohol (methanol or ethanol) in the presence of platinum compound (B) and a compound represented by formula (C). ##STR7## (In formulae (A) and (C), R.sub.1 represents a lower hydrocarbon group having 1 to 3 carbon atoms, and R.sub.2 and R.sub.3 each represent a hydrogen atom or a lower hydrocarbon group having 1 to 3 carbon atoms.)
The construction of the present invention is described in detail below.
Although the barium salt used in the present invention is not limited, preferable examples of the barium salt include barium hydroxides such as barium hydroxide anhydride, barium hydroxide octahydrate, and the like. Of these hydroxides, barium hydroxide octahydrate is preferably used from the viewpoint of ease of procurement.
Although the silver salt used in the present invention is not limited, silver sulfate is preferably used. The silver salt is used in an amount of 0.7 to 1.0 equivalent, preferably 0.9 to 0.99 equivalent, to platinum compound (B). If a small amount of silver sulfate is used, the reaction yield is decreased (Table 1). In the production method of the present invention, the amount of silver contained in the product is 1 ppm or less.
In the present invention, the barium salt can be used in an amount of 0.6 to 1.0 equivalent, preferably 0.75 to 0.95 equivalent, to platinum compound (B). Particularly, 0.9 to 0.95 equivalent of barium salt is preferably used. The amount of the barium hydroxide used significantly affects, particularly, the reaction yield and the amount of barium contained in the product (Table 2 below). With the use of an excess of barium hydroxide, barium is contained in a drug product, while with a small amount of barium hydroxide, the reaction yield is decreased. Although the theoretically n
REFERENCES:
patent: 5616613 (1997-04-01), Kawai et al.
Go Hata
Hideki Kawai
Takayuki Imaoka
Nazario-Gonzalez Porfirio
Toray Industries Inc.
LandOfFree
Method of producing platinum (II) complex does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of producing platinum (II) complex, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of producing platinum (II) complex will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-980470