JPS62226996A - Production of carboxylato(diamine)platinum - Google Patents

Abstract

PURPOSE:To readily obtain the titled compound useful as an antitumor agent in high yield at a low cost, by dissolving a dicarboxylic acid derivative and a platinate in water, adjusting the pH to a specific value with an inorganic base and adding and reacting a diamine derivative therewith. CONSTITUTION:A dicarboxylic acid derivative, e.g. oxalic acid, phenylmalonic acid, etc., and a platinate are dissolved in water and the pH is adjusted to 3-7 with an inorganic base, e.g. NaOH, KOH, etc. A diamine derivative, e.g. 1-amino-1-aminomethylcyclohexane, etc., is then added to the aqueous solution and reacted therewith, preferably at 50-150 deg.C for 0.5-10hr to afford the aimed compound, e.g oxalato(1-amino-1-aminomethylcyclohexane)platinum(II), etc.

Description

DETAILED DESCRIPTION OF THE INVENTION Part 1 of the present invention is carboquinrad(diamine)platinum(n)
Relating to a manufacturing method. More specifically, a diamine derivative is added to an aqueous solution in which a dicarboxylic acid derivative and a platinum salt are dissolved in water and the pH is adjusted from 3 to 7 using an inorganic base.
This is a method for producing carboxylate (diamine) platinum (II), characterized in that the reaction is carried out at 00'C.

Follower Juu1 0-Cisplatin (CI) DP by Senberg et al.
Discovery of antitumor activity of [Nature 22(-385(19)
[69)] Since then, research on platinum complexes with antitumor activity has been actively conducted, and many platinum complexes have been synthesized that have various adhesive properties, and their antitumor activity is also being investigated. Among these, platinum complexes containing diamine derivatives and dicarboxylic acid derivatives as ligands have particularly excellent antitumor activity. These platinum complexes are generally published in the Journal of Medicinal Chemistry (J, Med.

Chem, ), iL 1315 (1978), JP-A-59-139380, JP-A-54-48752, etc. This manufacturing method is as shown in the formula below.

(Formula 1) (Formula 2) O (wherein R1 to RIQ are the same or different and are hydrogen atoms, linear, branched or cyclic alkyl, aryl, alkaryl, aralkyl, alkenyl, hydroxy,
It is a group selected from alkoxy, aryloxy, nitro, amido, amino, halogen, sulfonic acid, and carboxylic acid, and two groups among R1 to RIQ may be combined to form a ring.

” indicates 0 or 1. Ru” R14 are the same or different and are hydrogen atoms, linear, branched or cyclic alkyl, aryl, alkaryl, aralkyl, alkenyl, hydroxy, alkoxy, aryloxy, nitro, amido, amino, halogen, sulfone It is a group selected from acids and carboxylic acids, and two groups among R11 to R14 may be combined to form a ring. m is ol
1 or 2, n represents O or 1, and Z represents a hydrogen atom or a metal salt. ) That is, dichloro(diamine)platinum (■
) (Formula 2), react this compound with silver nitrate to obtain dinitrato(diamine)platinum (■) (Formula 3), and further react this compound with various dicarboxylic acid derivatives or their metal salts (Formula 4). Various carboxylate (diamine) platinum (n)
This is a method to obtain (Equation 5).

! f　　　　　′′　　　.

The conventional manufacturing method described above has the following problems. In other words, ■ Using various diamine derivatives (Formula 1) as starting materials, the target compound carboxylate (diamine) platinum (■
) (Equation 5) required three steps and a considerable number of days for synthesis.

■Water used as a solvent in the process of synthesizing dinitrate(diamine)platinum (n) (formula 3) from dichloro(diamine)platinum (■) (formula 2) must be concentrated at a low temperature, and post-treatment is extremely difficult. It took time.

■Silver chloride produced in the process of synthesizing dinitrate(diamine)platinum (n) (formula 3) from dichloro(diamine)platinum (■) (formula 2) has fine particles and requires a lot of effort to remove. .

■Cost was high because silver nitrate was used.

■The yield was not good due to the large number of steps.

etc. Therefore, the present inventors have developed carboxylate (diamine) platinum (■
) (Equation 5), and by the following means, the method of the present invention was discovered and the above problems were solved.

The present inventors dissolved various dicarboxylic acid derivatives and platinates in water, added various diamine derivatives to an aqueous solution in which the I)H was adjusted from 3 to 7 with an inorganic base, and reacted at 0 to 100°C. Carboxylate (diamine) characterized by
A method for producing platinum (II) was established, the above-mentioned problems were solved, and the present invention was completed.

The manufacturing method of the present invention is as shown in the formula below.

(12,,112,, (121淋, -〇- (Formula 5) (In the formula, R1 to RIO are the same or different, hydrogen atoms, linear, branched or cyclic alkyl, alkaryl, aralkyl, alkenyl, hydroxy,
It is a group selected from alkoxy, aryloxy, nitro, amido, amino, halogen, sulfonic acid, and carboxylic acid, and two groups among R1 to Rho may be combined to form a ring.

! indicates O or 1. R+1 "R14 is the same or different and is a hydrogen atom, linear, branched or cyclic alkyl, aryl, alkaryl, aralkyl, alkenyl, hydroxy, alkoxy, aryloxy, nitro, amido, amino, halogen, sulfone A group selected from acids and carboxylic acids, and two groups of R11 to R14 may be combined to form a ring. m represents 0.1 or 2, and n represents 0 or 1.) Carboxylate(diamine)platinum(II) of the invention
) will be described in more detail.

Examples of various dicarboxylic acid derivatives represented by formula 7 include evaxalic acid, malonic acid, methylmalonic acid, ethylmalonic acid, phenylmalonic acid, benzylmalonic acid, hydroxymalonic acid, dimethylmalonic acid, diethylmalonic acid, dihydroxymalonic acid, 1゜1-cyclobutanedicarboxylic acid,
Succinic acid, 2-bromosuccinic acid, malic acid, itaconic acid, tartaric acid, 2,3-dibromosuccinic acid, dihydroxytartaric acid, maleic acid, dibromomaleic acid, dihydroxymaleic acid, phthalic acid, hemimellitic acid, trimellitic acid, glutaric acid acid, diglycolic acid, iminodiacetic acid, and the like.

Examples of platinates include lithium salts, potassium salts, and sodium salts. 1) Examples of the inorganic base used to adjust H include sodium hydroxide, potassium hydroxide, calcium hydroxide, and the like.

Various diamine reading conductors represented by formula 1 include ethylene diamine derivatives, propylene diamine derivatives, such as cyclohexane diamine derivatives, cyclopentanediamine derivatives, aminoalkylpyridine derivatives, aminoalkylpiperidine derivatives, aminoalkylpyrrolidine derivatives, aminoalkyl azetidine derivatives, Examples include aminoalkylaziridine derivatives and aminoalkylmorpholine derivatives.

Preferably, the cyclohexanediamine derivative is 1-
Examples include amino-1-aminomethylcyclohexane, 1,2-diaminocyclohexane, and 1-amino-2-aminomethylcyclohexane. Preferred examples of the cyclopentanediamine derivative include 1-amino-1-aminomethylcyclopenkune, 1. Examples include 2-diaminocyclopentane and 1-amino-2aminomethylcyclopentane. Preferred aminoalkylpyridine derivatives include 2-aminomethylpyridine, 2-(1-aminoethyl)pyridine, 2-(1-amino-n-propyl)pyridine, 2-(1-amino-n-butyl)pyridine, 2
-(1-amino-n-pentyl)pyridine, 2-(N-
methylaminomethyl)pyridine, 2-aminomethyl-6
-methylpyridine, 2-(2-aminoethyl)pyridine, 2-(N-methylaminoethyl)pyridine, and the like. Preferred aminoalkylpiperidine derivatives include 1-(2-aminoethyl)piperidine, 1-(3
-amino-n-propyl)piperidine, 2-aminomethylpiperidine, 2-aminomethyl-1-ethylpiperidine, 2-aminomethyl-1-methylpiperidine, 2-(1
-aminoethyl)piperidine, 2-(1-amino-n-
propyl)piperidine, 2-(1-amino-n-butyl)piperidine, 2-(1-amino-n-pentyl)piperidine, 2-(N-iso-propylaminomethyl)
piperidine, 2-(2-aminoethyl)piperidine,
Examples include 1,2-dipiperidinoethane. Examples of aminoalkylpyrrolidine derivatives include 1-(2-aminoethyl)pyrrolidine, 1-(3-amino-n-propyl)pyrrolidine, 2-aminomethylpyrrolidine, 2-(N-methylaminomethyl)pyrrolidine, 2-(N-methylpyrrolidine), and 2-(N-methylaminomethyl)pyrrolidine. -ethylaminomethyl)pyrrolidine, 1-methyl-2-(N-methylaminomethyl)pyrrolidine, 2-aminomethyl-1-methylpyrrolidine, 2-aminomethyl-1=ethylpyrrolidine, 2-aminomethyl-1, 5-dimethylpyrrolidine, 2-(1-aminoethyl)pyrrolidine, 2-(2-aminoethyl)-1-methylpyrrolidine, 1-(2-aminoethyl)-2methylpyrrolidine, 1-(2-aminoethyl) -3-methylpyrrolidine, 1-(2-aminoethyl)-2,3-dimethylpyrrolidine, 1-(2-N-
ethylaminoethyl)pyrrolidine, 1-(2-N-methylaminoethyl)-2-methylpyrrolidine, 1-(2
-N,N-dimethylamineethyl)pyrrolidine, 1-
(2-N,N-diethylaminoethyl)pyrrolidine, 2
-Aminomethyl-3-methylpyrrolidine, 2-aminomethyl-4-methylpyrrolidine, 1-methyl-2-N-methylaminomethylpyrrolidine, 2-N-methylaminomethyl-3-methylpyrrolidine, 2-N,N -dimethylaminomethylpyrrolidine, 2-N,N-diethylaminomethylpyrrolidine, and the like. Preferred aminoalkyl azetidine derivatives include 1-(2-aminoethyl) azetidine and 2-aminomethyl azetidine. Preferably, the aminoalkylaziridine derivative is
Examples include 1-(2-aminoethyl)aziridine and 2-aminomethylaziridine. Preferably, the aminoalkylmorpholine derivative is 4-(2-aminoethyl)
Morpholine, 4-(3-amino-n-propyl)morpholine, 4-(2-aminoethyl)-2-methylmorpholine, 4-(2-aminoethyl)-3-methylmorpholine, 4-(2-N- methylaminoethyl)morpholine, 4-(2-N-ethylaminoethyl)morpholine, 2-methyl-4-(2-N-methylaminoethyl)morpholine, 4-(2-N,N-diethylamineethyl)
Examples include morpholine. Other examples include 2-aminomethylimidazole, 2-(2-aminoethyl)imidazole, 2-aminomethylbenzimidazole, 2-aminomethyloctahydrobenzimidazole, and 8-aminodecahydroquinoline.

These also include optically active forms thereof.

Platinates and 1 to 5 times the mole of the dicarboxylic acid derivative (Formula 5) are dissolved in water, the pH is adjusted to 3 to 7 with an inorganic base, and 1 mole of the diamine derivative (Formula 1) is added to this solution. In addition, the temperature ranges from O to 100°C, preferably from 50 to 100°C.
The reaction is carried out at a temperature of 0.degree. C. for 10 hours under stirring. After completion of the reaction, a slight amount of precipitated insoluble matter is removed using a Millipore filter or the like, and the filtrate is compressed under reduced pressure with Fl, and the precipitated reaction product is collected by filtration. After washing the product with water, methyl alcohol, ethyl alcohol, etc., it is dried under pressure at a temperature ranging from 10.5 to 5 hours, usually at a temperature of 0 to 80°C.

By the above production method to obtain the target compound, the conventional production method required 3 steps, but the production method of the present invention shortens it to 1 step, and the synthesis process, which used to take a considerable number of days, is reduced to 0.5 steps. Since then, it has been held every 10 hours.

■In the conventional production method, the water used as a solvent in the process of synthesizing dinitrate(diamine)platinum (■) (Formula 3) from dichloro(diamine)platinum (■) (Formula 2) must be concentrated at low temperatures. However, in the production method of the present invention, the reaction is carried out without going through this step, so that the work in this step is omitted, and the time required is greatly shortened.

■In the conventional production method, silver chloride generated in the process of synthesizing dinitrate(diamine)platinum (■) (23) from dichloro(diamine)platinum (■) (Formula 2) must be removed using a Millipore filter, etc. Although this process is normally extremely time-consuming, in the production method of the present invention, the reaction is carried out without going through this process, so this process is omitted and the time required is greatly reduced. .

(2) The conventional method required the use of silver nitrate, resulting in high costs, but the production method of the present invention eliminates the need for this, leading to cost reductions.

(2) In the conventional method, the yield was not good because of the large number of steps, but in the method of the present invention, the yield was very good.

The above problems were solved and the manufacturing method of the present invention was completed.

Specifically, the target carboxylate(diamine)platinum derivative (■) (formula 5) obtained by the above-mentioned production method of the present invention includes oxalato (or malonato, methylmalonato, ethylmalonato, phenylmalonato, benzylmalonato). , hydroxymalonato, dihydroxymalonato, 1,1-cyclobutanedicarboxylate, succinate, dihydroxymalonato, 1,2-cyfurosuccinato, dibromomaleate, glutarad, diglycolate, iminosiasect,
Pyrazine-2,3-dicarboxylate (same below) (1-
Amino-1-aminomethylcyclohexane)platinum(n), Oxalato(1,2-diaminocyclohexane)platinum(II), Oxalato(1-amino-2-aminomethylcyclohexane)platinum(n), Oxalato(1-amino- 1-aminomethylcyclopentane) platinum (n) Oxalato (1,2-diaminocyclopentane) platinum (II), Oxalato (1-amino-2-aminomethylcyclopentane) platinum (n), Oxalato (2-amino methylpyridine) platinum (
n), Oxalato[2-(1-aminoethyl)pyridine]platinum(II), Oxalato[2-(1-amino-n-propyl)pyridinecoplatinum(II), Oxalato[2-(1-amino-n-n) -butyl)pyridinecoplatinum (n), Oxalato[2-(1-amino-n-pentyl)pyridine]platinum (n), Oxalato[2-(N-methylaminomethyl)pyridinecoplatinum (n), Oxalato( 2-aminomethyl-6-methylpyridine)
Platinum (n), Oxalato[2-(2-aminoethyl)pyridine]bratinum(n), Oxalato[2-(N-methylaminoethyl)pyridine]bratinum(n), Oxalato[1-(2-aminoethyl) oxalato[1-(3-amino-n-propyl)piperidine]platinum(n), oxalato(2-aminomethylpiperidine)platinum(n), oxalato(2-aminomethyl-1-ethyl Piperidine) Platinum(II), Oxalato[2-(1-aminoethyl)piperidine Coplatinum(n), Oxalato[2-(1-amino-rl-propyl)piperidine Cobratinum(II), Oxalato[2-(1 -amino-n-butyl)piperidinecoplatinum (n), Oxalato[2-(1-amino-n-pentyl)piperidinecoplatinum (II), Oxalato[2-(N-iso-propylaminomethyl)piperidinecoplatinum (II), Platinum (n), Oxalato [2-(
2-aminoethyl)piperidine]platinum (n), oxalato(1,2-dipiperidinoethane)platinum(II), oxalato[1-(2-aminoethyl)pyrrolidine]platinum(n), oxalato[1- (3-Amino-n-propyl)pyrrolidinecoplatinum (n), Oxalato(2-aminomethylpyrrolidine)platinum(II), Oxalato[2-(N-methylaminomethyl)pyrrolidinecoplatinum(II), Oxalato[ 2-(N-ethylaminomethyl)pyrrolidine]platinum (n), oxalato[1-methyl-2-(N-methylaminomethyl)pyrrolidine]platinum (n), oxalato(2-
aminomethyl-1-methylpyrrolidine) platinum (n
), Oxalato(2-aminomethyl-1-ethylpyrrolidine)platinum(n), Oxalato(2-aminomethyl-1,5-dimethylpyrrolidine)platinum(n), Oxalato[2-(1-aminoethyl)pyrrolidine ] platinum (n), oxalato [2-(2-aminoethyl)-1-methylpyrrolidine coplatinum (II), oxalato [1-(2
-aminoethyl)-2-methylpyrrolidinecoplatinum(II), oxalato[1-(2-aminoethyl)-3
-Methylpyrrolidine cobratinum (n), oxalato[1-(2-aminoethyl)-2,3-dimethylpyrrolidine coplatinum (n), oxalato[1-
(2-N-ethylaminoethyl)pyrrolidine coplatinum (n), oxalato[1-(2-N-methylaminoethyl)-2
-methylpyrrolidine] platinum (n), oxalato [
1-(2-N,N-dimethylaminoethyl)pyrrolidine coplatinum (n), oxalato[1-(2-N,N-
diethylaminoethyl)pyrrolidine coplatinum (II
), oxalato(2-aminomethyl-3-methylpyrrolidine)platinum(n), oxalato(2-aminomethyl-4-methylpyrrolidine)platinum(II), oxalato[1-methyl-2-(N-methylaminomethyl) ) pyrrolidine] platinum (n), oxalato [2-
(N-methylaminomethyl)-3-methylpyrrolidine]
Platinum (n), Oxalato (2-N, N-dimethylaminomethylpyrrolidine) Platinum (n), Oxalato (3-N, N-diethylaminomethylpyrrolidine) Platinum (n), Oxalato [1-(2-aminoethyl) azetidinecoplatinum (If), oxalato (2-aminomethylazetidine) platinum (n), oxalato [1-(2-aminoethyl)aziridine] bratinum (II), oxalato (2-aminomethylaziridine) platinum ( n), Oxalato[4-(2-aminoethyl)morpholinecoplatinum (n), Oxalato[4-(3-amino-n-propyl)morpholinecoplatinum (IF), Oxalato[4-(2-aminoethyl)] -2-methylmorpholine] platinum (n), oxalato[4-(2-aminoethyl)-3-methylmorpholine]platinum (■), oxalato[4-(2-N-methylaminoethyl)morpholine]platinum ( n), Oxalato[4-(2-N-ethylaminoethyl)morpholinecoplatinum (n), Oxalato[2-methyl-4-(2-N-methylaminoethyl)morpholinecoplatinum (n), Oxalato[
4-(2-N,N-diethylaminoethyl)morpholinecoplatinum(II), oxalato(2-aminomethylimidazole)platinum(n), oxalato[2-(2-aminoethyl)imidazole)
Platinum (II), Oxalato (2-aminomethylbenzimidazole) Platinum (II), Oxalato (2-aminomethyloctahydrobenzimidazole) Platinum (II), Oxalato (8-aminodecahydroquinoline) Platinum (■), etc. can be mentioned.

These also include optically active forms thereof.

The platinum complex of the target compound represented by formula 4 obtained by the production method of the present invention is very useful as an antitumor agent.

The present invention will be described below with reference to Examples, but the present invention is not limited thereto.

1.80 g (0,045 mol) of sodium hydroxide is dissolved in 200 ml of water, and 4.15 g (0,01 mol) of platinum (n) botanium chloride and 1,
Add and dissolve 4.32 g (0.03 mol) of 1-cyclobutanedicarboxylic acid. At this time, the pH of the solution is approximately 5.4 (
23°C). Immediately after adding 1.00 g (0.01 mol) of (R)-2-aminomethylpyrrolidine to this solution and stirring at 90°C for 4 hours, the slightly precipitated insoluble matter was removed using a Millipore filter (0.22 μm). and remove it. The obtained filtrate was concentrated under reduced pressure to 20 ml and then stirred at room temperature for 1 hour to precipitate a white crystalline solid. The generated solid was collected by filtration, washed with water, and then dried under reduced pressure at 60°C for 3 hours.
(R)-1,1-cyclobutane dihydropoxylate (2-
(aminomethylpyrrolidine) platinum(II) 3.
15 g (yield 72%) was obtained. Melting point 248-257℃
(Disassembly).

In the same manner as in Example 1, 1,1-cyclobutane dihydropoxylate (2-aminomethylpyrrolidine)platinum (■) was prepared using 2-aminomethylpyrrolidine (yield 74%).
I got it.

In the same manner as in Example 2, (S)-1,1-cyclobutanedicarboxylate(2-aminomethylpyrrolidine)platinum (■
) (yield 75%) was obtained.

misfortune The following compounds were obtained in the same manner as in Examples 1 to 3.

1) 1.1-cyclobutanediylupoxylate [2-(1
-aminoethyl)pyrrolidine] platinum (■) (yield 70%) 2) 1.1-cyclobutanedicarboxylate (2-N-
methylaminomethylpyrrolidine) platinum (■) (yield 79%) 3) 1.1-cyclobutanedihydrupoxylate (2-N-
ethylaminomethylpyrocillin) platinum (■) (yield 82%) 4) 1.1-cyclobutanedicarboxylate (2-aminomethyl-1-methylpyrrolinone) platinum (■) (
5) 1.1-cyclobutane dicarboxylate [1-methyl-2-(N-methylaminomethyl)pyrrolidine coplatinum (■) (yield 75%) Ei) 1.1-cyclobutane dicarboxylate Lato(2-aminomethyl-1-ethylpyrrolidine)platinum (■) (yield 79%) 7) 1.1-Cyclobutanedihydrupoxylate(2-aminomethylazetidine)platinum(II) (yield 81%
) 8) Oxalato (2-aminomethylpyrrolidine) platinum (■) (yield 72%) 9) Oxalato [2-(1-aminoethyl)pyrrolidine] platinum (■) (yield 73%) 10) Oxalato (2 -N-methylaminomethylpyrrolidine)platinum (■) (yield 75%) 11) Oxalato(2-N-ethylaminomethylpyrrolidine)platinum (■) (yield 75%)
9%) 12) Oxalato [1-methyl-2-(N-methylaminomethyl)pyrrolidine coplatinum (n) (yield 74%) 13) Oxalato [2-(2-aminoethyl)-1-methylpyrrolidine] Platinum (■) (yield 76%) 14) Oxalato (2-aminomethyl-1-ethylpyrrolidine) Platinum (■) (yield 71%) +5) Oxalato (2-aminomethyl-1,5-dimethylpyrrolidine) Platinum (■) (Yield: 78%) Tips and Tricks 1 Dissolve 0.90 g (0,0225 mol) of sodium hydroxide in 100 ml of water, and add 2.08 g (0,005 mol) of platinum (II) botium chloride. ) and 1,1-cyclobutanedicarboxylic acid2. leg(0,
015 mol) and dissolve. At this time, the pH of the solution is approximately 5.4 (23°C). 0.54 g (0.005 mol) of 2-aminomethylpyridine was added to this solution, which was stirred for 4 hours using a Cini 900c, and a slight amount of precipitated insoluble matter was removed using a Millipore filter (0.22 μm). The obtained filtrate was concentrated to 20 ml under reduced pressure and then stirred at room temperature for 1 hour to precipitate a white crystalline solid. The generated solid was collected by filtration, washed with water, and dried under reduced pressure at 60°C for 3 hours to obtain 1.45 g of 1,1-cyclobutanedicarboxylate (2-aminomethylpyrrolidine) platinum (II).
(yield: 65%).

Melting point: 250-275°C (decomposed) [Real] 1.80 g (0,045 mol) of sodium hydroxide is dissolved in 200 ml of water, and 4.15 g (0,01 mol) of platinum (II) botanical chloride is dissolved in this. ) and 3.78 g (0.03 mol) of oxalic acid (dihydrate) were added and dissolved. At this time, the pH of the solution was approximately 4.0 (23℃
). Add 1.0 2-aminomethylpyridine to this solution.
Add 8g (0.01 mol) and immediately heat to 90°C for 4 hours.
After about 11 hours, a white crystalline solid precipitates out. The generated solid was collected by filtration, washed with water, and then dried under reduced pressure at 60° C. for 3 hours to obtain 2.89 g (yield: 74%) of oxalato(2-aminomethylpyridine)platinum (n). Melting point>300
°C Jitton L [Dissolve 0.180 g (0,0045 mol) of sodium hydroxide in 20 ml of water, and add 0.415 g (0°001 mol) of platinum (n) potassium chloride and 354 g (0.0 mol) of methylmalon mo. ,003 mol) and dissolve. The pH at this time is about 5.4 (23°C). Add 0.108 g of 2-aminomethylpyridine to this solution.
(0,001 mol) and immediately stirred at 90° C. for 4 hours to precipitate a white crystalline solid. The generated solid was collected by filtration, washed with water, and dried under reduced pressure at 6 to 100°C for 3 hours.
0.302 g (yield 72%) of methylmalonato(2-aminomethylpyridine)platinum(II) was obtained.

Melting point 290-300℃ (decomposition) Ten 1 Death Hero- The following compounds were obtained in the same manner as in Examples 5-6.

1) Malonato (2-aminomethylpyridine) platinum (■) (yield 75%) 2) Ethylmalonato (2-aminomethylpyridine) platinum (■) (yield 76%) 3) Oxalato [2-(1-amino) ethyl)pyridine] platinum (■) (yield 82%) 4) Hydroxymalonato [2-(1-aminoethyl)pyridine] platinum (■) (yield 83%) 5) 1,1-cyclobutane dicamboquinato [2-(1-aminoethyl)pyridinecoplatinum (■) (yield 75%) 6) Malonato[2-(1-aminoethyl)pyridinecoplatinum (■) (yield 81%) 7) Oxalato[2 -(1-amino-n-propyl)
Pyridine coplatinum (■) (yield 73%) 8) 1.1
-cyclobutane dicarboxylate [2-1-amino-n
-propyl) pyridinecoplatinum (■) (yield 79%
) 9) Hydroxymalonato [2-(1-amino-n-
Propyl) pyridine coplatinum (■) (yield 85%) 1F and 熢采 As described above, the production method of the present invention is an excellent method that solves each of the problems in the conventional production method, and =29- The desired carboxylate (diamine) platinum (II) can be obtained efficiently in a short time.

Claims (1)

[Claims] 1) Carboxylate (diamine) platinum, which is characterized in that dicarboxylic acid derivatives and platinates are dissolved in water, the pH is adjusted to 3 to 7 with an inorganic base, a diamine derivative is added to an aqueous solution, and the reaction is carried out at 0 to 100°C. manufacturing method.