# US 7,608,730 B2 · Process for the preparation of an anti-tumor platinum (II)—complex

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,608,730 B2
- Document ID: US7608730B2
- Status: Granted
- Kind: B2
- Application number: 10/588,397
- Filed: 2004-02-05
- Published: 2008-08-28
- Granted: 2009-10-27
- Earliest claimed: 2004-02-05
- Assignees: Fresenius Kabi Oncology Limited
- Inventors: Golak Chandra Maikap; Bhagat Raj; Pradipta Kumar; Kannan Vivekanandan; Chandrakant Belwal
- Web page: https://patentgrep.com/patent/US7608730B2

## CPC

- C07F 15/0093: {without a metal-carbon linkage}
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

We disclose here processes for making Platinum complex of general formula (I) where in, the conformation of 1,2-diaminocyclohexane is cis, trans-l or trans-d isomer and R1 and R2 combinedly make dicarboxylic acid having formulae (II), (III) and (IV), here in, the two carboxylic acid groups are on the same or on vicinal carbon atoms, n is zero or an integer ranging from 1 to 5 and R3 is either hydrogen or a substituent with electron withdrawing or electron releasing effects exemplified by alkoxy, halo, and nitro groups by reacting a compound of formula M2PtX4 wherein X represents halogen atom such as Cl or Br or thiocyanate with (i) 1,2-diaminocyclohexane (ii) source of silver ion selected from a silver compound containing divalent anion in presence of a corresponding carboxylic acid of formula (II) or (III) or (IV) to get the compound of formula (I), purifying the said compound by treating with alkali metal iodide and isolating the title compound by any conventional methods. The preparation of the said compound involves, for the first time, the intermediate formation of cis-Diiodo-trans-l-1,2-diaminocyclohexane platinum(II) and biscarboylato-trans-l-1,2-diaminocyclohexane platinum(II).

## Claims

### Claim 1

A process for the preparation of a platinum (II) complex compound of general formula (I)
wherein the conformation of 1,2-diaminocyclohexane is cis, trans-(l) or trans-(d) isomer and R1 and R2 combinedly make dicarboxylic acid anion having formulae II, III and IV
wherein n is zero or an integer ranging from 1 to 5 and R3 is H, alkoxy, halo or a nitro group comprising the steps of:
i) reacting a compound of formula M2PtX4 wherein X represents thiocyanate or a halogen atom selected from Cl, Br, and I with 1,2-diaminocyclohexane to give a compound of formula (V);
ii) reacting the compound of formula (V) of step i), with a source of silver ion selected from a silver compound containing divalent anion in presence of an aliphatic carboxylic acid or an aliphatic or aromatic sulphonic acid to give compound of formula (VI)
wherein R is —O—CO—R′ or O—SO2—R′, wherein R′ is H, an alkyl or an aryl group; and
iii) reacting the compound of formula (VI) of step ii), with a dicarboxylic acid or its salts to give the object platinum (II) complex compound of formula (I).

### Claim 2 (depends on 1)

A process according to claim 1, wherein the conformation of 1,2-diaminocyclohexane is trans-(l).

### Claim 3 (depends on 1)

A process according to claim 1, wherein the Platinum (II) complex compound is cis-oxalato-trans-(l)-1,2 diamino cyclohexane Platinum.

### Claim 4 (depends on 1)

A process according to claim 1, wherein in the compound of formula M2PtX4, M represents sodium or potassium and X represents Cl, Br, I or thiocyanate.

### Claim 5 (depends on 4)

A process according to claim 4, wherein the compound of formula M2PtX4 is Potassium tetrachloroplatinate.

### Claim 6 (depends on 1)

A process according to claim 1, wherein the source of silver ion is silver carbonate or silver oxide.

### Claim 7 (depends on 1)

A process according to claim 1, wherein the source of silver ion is silver oxide.

### Claim 8 (depends on 1)

A process according to claim 1, wherein the aliphatic carboxylic acid is straight chained or branched having 1 to 5 carbon atoms.

### Claim 9 (depends on 1)

A process according to claim 1, wherein the aliphatic carboxylic acid is acetic acid.

### Claim 10 (depends on 1)

A process according to claim 1, wherein the aliphatic sulphonic acid is straight chained or branched having 1 to 5 carbon atoms.

### Claim 11 (depends on 7)

A process according to claim 7, wherein the aliphatic sulphonic acid is methanesulphonic acid.

### Claim 12 (depends on 1)

A process according to claim 1, wherein the dicarboxylic acid salt is dipotassium oxalate.

### Claim 13 (depends on 1)

A process according to claim 1, wherein the mole ratio of M2PtX4 to 1,2-diaminocyclohexane is between 1.0 and 1.2.

### Claim 14 (depends on 1)

A process according to claim 1, wherein step i) is carried out at a temperature of between 15° C. and 40° C.

### Claim 15 (depends on 1)

A process according to claim 1, wherein the mole ratio of the source of silver ion to the compound of formula (V) is between 1.0 and 2.2.

### Claim 16 (depends on 1)

A process according to claim 1, wherein the step ii) is carried out at a temperature of between 40° C. and 80° C.

### Claim 17 (depends on 1)

A process according to claim 1, wherein the mole ratio of the source of silver ion to the aliphatic carboxylic acid or the aliphatic/aromatic sulphonic acid is between 1.0 and 1.2.

### Claim 18 (depends on 1)

A process according to claim 1, wherein the mole ratio of compound of formula (VI) to the dicarboxylic acid or its salts is between 0.7 and 1.2.

### Claim 19 (depends on 1)

A process according to claim 1, wherein the step iii) is carried out at a temperature of between 50° C. and 75° C.