[ CAS No. 61825-94-3 ] {[proInfo.proName]}

Name: 61825-94-3|Oxalato(trans-l-1,2-cyclohexanediamine)platinum(II)|98%
Brand: Ambeed
SKU: A100048
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Quality Control of [ 61825-94-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 61825-94-3 ]

Product Details of [ 61825-94-3 ]

CAS No. :	61825-94-3	MDL No. :	MFCD00866327
Formula :	C₈H₁₄N₂O₄Pt	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	DRMCATBEKSVAPL-BNTLRKBRSA-N
M.W :	397.29	Pubchem ID :	9887053
Synonyms :	Lipoxal;RP 54780;SR96669.;Code names: JM83;LOHP;Abbreviations: 1OHP;Eloxatine;Dacplat;US brand name: Eloxatin Foreign brand names: Dacotin;oxalatoplatinum;oxalatoplatin;diaminocyclohexane oxalatoplatinum;NSC 266046	Chemical Name :	Oxalato(trans-l-1,2-cyclohexanediamine)platinum(II)

Calculated chemistry of [ 61825-94-3 ]

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.75
Num. rotatable bonds :	0
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	54.27
TPSA :	104.64 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.99 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.04
Log Po/w (WLOGP) :	-1.55
Log Po/w (MLOGP) :	-1.1
Log Po/w (SILICOS-IT) :	-1.52
Consensus Log Po/w :	-0.63

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.96
Solubility :	0.437 mg/ml ; 0.0011 mol/l
Class :	Soluble
Log S (Ali) :	-2.83
Solubility :	0.591 mg/ml ; 0.00149 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.6
Solubility :	9.89 mg/ml ; 0.0249 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	4.89

Safety of [ 61825-94-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P201-P202-P261-P264-P271-P272-P280-P302+P352-P304+P340-P305+P351+P338-P308+P313-P362+P364-P403+P233-P501	UN#:	N/A
Hazard Statements:	H315-H317-H319-H335-H351	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 61825-94-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 61825-94-3 ]
Downstream synthetic route of [ 61825-94-3 ]

[ 61825-94-3 ] Synthesis Path-Upstream 1~19

1
[ 10025-99-7 ]
[ 20439-47-8 ]
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
20%	With silver(l) oxide In water at 90 - 100℃; for 10 - 12 h;	A mixture of 50 g of potassium tetrachloroplatinate (0.12 mol), trans-l-1,2-diamino cyclohexane, 13.74 g (0.12 mol), 25.15 g of silver oxide (0.10 mol) and 13.66 g of oxalic acid dihydrate (0.10 mol) were heated together in 3 liters of DM water at 90-100° C. for 10-12 h. The reaction mixture was cooled to 50° C. filtered through celite. The filtrate was treated with 0.5 g of potassium iodide at 30° C. for 10-12 h in dark. Then again filtered through celite. The filtrate was treated with activated carbon to remove colour. Removal of 2.8 liters of water at 60° C. under vacuum produces oxaliplatin as a white crystalline solid (10 g, 20percent).

Reference： [1] Patent: US2008/207935, 2008, A1, . Location in patent: Page/Page column 7

2
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
62.9%	Stage #1: at 20 - 45℃; for 2.08333 h; Stage #2: With potassium hydroxide In water at 20℃; for 4 h;	A mixture of 3,88 g of fine powdered DACHPtCI₂ 98percent (10 mmol), 1.55 g purified Celite, 3.41 g AgNO₃ 99.5percent (20 mmol) and 27 ml pu- rified water was intensively stirred 5 minutes at room temperature and then 2 hours at 45⁰C. The suspension was cooled to 3⁰C and then filtered through the plate with active charcoal. The crude acidic filtrate had the content of silver ions 0.0018 mass.percent ,i.e. 18 p.p.m. 0.19 g of Smopex-101 was added to the crude filtrate and the sus- pension was stirred 1 hour at room temperature. The solid fraction was then removed by filtration. The purifying procedure with <n="16"/>Smopex-101 was repeated once again and the purified solution was then filtered through an ultrafilter with the porosity 0.22 μm. 1.27 g oxalic acid dihydrate 99.5percent (10 mmol) was added to the purified solution, pH value was adjusted to 2.9 by means of 40percent solution of KOH₁ the mixture was stirred 4 hours at room temperature and the resulting suspension was cooled to 3⁰C. The final solid oxaliplatin was separated by filtration, washed four times with 5 ml ice water and four times with 5 ml ethanol. Oxaliplatin was dried under nitrogen flow at 40⁰C to the constant weight. The yield of oxaliplatin was 2.80 g (70.5percent based on starting DACHPtCI₂). The appearance of the product was white. The content of silver was less than 0.00005 mass percent, i.e. 0.5 p.p.m., the content of oxalic acid was 0.04percent, the content of platinum(ll) diaqua-complex was 0.08percent, and the total content of related impurities was 0.22percent (by HPLC method).; Example 2; The same procedure according to Example 1 with exception that 0.39 g Dowex 50x8 in H-cycle was used instead of 0.19 g Smopex- 101 for purifying of the crude filtrate and that time of purification was 2 hours instead of 1 hour.The yield of oxaliplatin was 2,50 g (62.9percent based on startingDACHPtCI₂). The appearance of the product was white. The content of silver was 0.0001 mass percent, i.e. 1 p.p.m., the content of oxalic acid was 0,04percent, the content of platinum(ll) diaqua-complex was 0.09percent, <n="17"/>and the total content of related impurities was 0.25percent (by HPLC method).; Example 3 (comparative, without Celite); The same procedure according to Example 1 with exception that no Celite was used in the procedure. The crude acidic filtrate had the content of silver ions 0.2500 mass.percent, i.e. 2500 p.p.m.The yield of oxaliplatin was 2.60 g (65.5percent based on starting DACHPtCI₂). The appearance of the product was white. The content of silver was 0.0220 mass percent, i.e. 220 p.p.m.
54%	Stage #1: With silver nitrate In water at 20℃; for 70 h; Stage #2: With tetraethylammonium iodide In water for 16 h; Stage #3: for 4 h;	Silver nitrate (80.6 g) is added to a suspension of 88.9 g of (SP-4-2)-dichloro-[(1R,2R)-1,2-cyclohexanediamine-N,N']platinum(II) in 900 ml of water, and the obtained mixture is stirred for 70 hours at room temperature, in the dark. The insoluble portion is filtered off of the reaction mixture, and this portion is washed with 100 ml of water. Tetraethylammonium (2,5 g) iodide is added to the filtrate mixed with the washing liquid, and the obtained mixture is stirred for 16 hours. Activated charcoal (0,6 g) is added to the reaction mixture, and the mixture is filtered. Oxalic acid dihydrate (29, 5 g) is added to the obtained filtrate under stirring, and 4 hours later the precipitated oxaliplatin is filtered off. The filter cake is washed with 30 ml of water and 500 ml of ethanol divided into five portions, and the raw product is dried in a vacuum drier. After recrystallisation from water, the separated oxaliplatin is washed with 30 ml of water and 400 ml of ethanol divided into five portions, and dried in a vacuum drier at 70 °C up to a constant weight. Oxaliplatin is obtained in a yield of 50,2 g (54 percent of the theoretical yield based on the starting (SP-4- 2)-dichloro-[(1R,2R)-1,2-cyclohexanediamine-N,N']platinum(II). The obtained oxaliplatin contains less than 0.001 percent by weight of alkali metals, less than 0.0002 percent by weight of silver, and less than 0.001 percent of nitrates (NO3). The content of oxalic acid is lower than 0.01 percent by weight.
40.3%	Stage #1: at 20℃; for 70 h; Stage #2: at 20℃; for 4 h;	A mixture 3.88 g of fine powdered DACHPtCI₂ 98percent (10 mmol), 3.41 g AgNO₃ 99.5percent (20 mmol) and 27 ml purified water was intensively stirred 70 hours at room temperature. The suspension was cooled to 3⁰C and then filtered through the plate with active charcoal. The crude acidic filtrate had the content of silver ions 0.0060 mass.percent ,i.e. 60 p.p.m. 0,17 g potassium iodide (1 mmol) was added to the filtrate and stirred for additional 15 hours. Active charcoal in an amount of 0,1 g was then added, the suspension was stirred for another 1 hour and then the solid fraction was removed by filtration. The purified solution was filtered through an ultrafilter with the porosity 0.22 μm. <n="18"/>1.27 g oxalic acid dihydrate 99.5percent (10 mmol) was added to the purified solution, the mixture was stirred 4 hours at room temperature and the resulting suspension was cooled to 3⁰C. The final solid ox- aliplatin was separated by filtration, washed four times with 5 ml ice water and four times with 5 ml ethanol. Oxaliplatin was dried under nitrogen flow at 4O⁰C to the constant weight.The yield of oxaliplatin was 2,51 g (63.2percent based on starting DACHPtCI₂). The content of silver was 0.0004 mass percent, i.e. 4 p.p.m.. but the appearance of the product was light yellow.The light yellow oxaliplatin was re-crystallized from hot water (1 mass part of oxaliplatin and 42 mass part of water). The hot solution was ultrafiltered, cooled to 3⁰C, the solid product was separated by filtration and washed three times with 5 ml of ice water. The oxaliplatin was dried under nitrogen flow at 4O⁰C to the constant weight. The yield was 1 ,60 g (40.3percent based on the starting DACHPtCI₂). The appearance of the product was white. The content of silver was 0.0002 mass percent, i.e. 2 p.p.m., the content of oxalic acid was 0.03percent, the content of platinum(ll) diaqua-complex was 0.10percent, and the total content of related impurities was 0.21percent (by HPLC method).

Reference： [1] Patent: WO2007/140804, 2007, A1, . Location in patent: Page/Page column 14-16
[2] Patent: WO2005/35544, 2005, A1, . Location in patent: Page/Page column 6-7
[3] Patent: WO2007/140804, 2007, A1, . Location in patent: Page/Page column 16-17

3
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Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: With acetic acid; silver(l) oxide In water at 80 - 90℃; for 4 h; Stage #2: at 60℃; for 5 h;	Cis-diiodo-trans-l-1,2-diaminocyclohexane (50 g, 0.09 mol) prepared as per example-1 was heated with stirring in 2.5 liters of DM water at 80-90° C. with acetic acid (10.66 g) and silver oxide, 20.88 g (0.09 mol). The reaction was complete in 4 h (by HPLC). The reaction mixture was filtered through celite and the clear filtrate was treated with dipotassium oxalate monohydrate, 14.9 g (0.08 mmol) at 60° C. under stirring.The reaction was continued at this temperature for 5 h and then subsequent work up produced 21.44 g of oxaliplatin (60percent).

Reference： [1] Patent: US2008/207935, 2008, A1, . Location in patent: Page/Page column 8

4
[ 61848-66-6 ]
[ 15843-43-3 ]
[ 61825-94-3 ]

Reference： [1] Inorganica Chimica Acta, 2013, vol. 401, p. 64 - 69

5
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[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
38%	With silver(l) oxide In water at 60 - 100℃; for 13 - 14 h;	A mixture of silver oxide (27.14g, 0.1 lmol) and oxalic acid dihydrate (14.75g, 0.1 lmol) and cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II), 50g (0. 13mol) prepared as per example-2 in 2.5liters of DM water was heated at 90-100 C. for 1-2 hours. Temperature of the reaction mixture was brought down to 60 C. The reaction was continued for 12h at this temperature. Completion of the reaction was checked by HPLC. The reaction mixture was filtered through celite and the filtrate treated with 0.5g of potassium iodide as in example-3. Carbon treatment followed by water removal produces oxaliplatin (20g, 38percent).

Reference： [1] Patent: WO2005/75489, 2005, A1, . Location in patent: Page/Page column 14; 22

6
[ 1113-38-8 ]
[ 61825-94-3 ]

Reference： [1] Patent: US2005/197389, 2005, A1, . Location in patent: Page/Page column 2; 3

7
[ 61848-66-6 ]
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
38%	With silver(l) oxide In water at 60 - 100℃; for 13 - 14 h;	A mixture of silver oxide (27.14 g, 0.11 mol) and oxalic acid dihydrate (14.75 g, 0.11 mol) and cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II), 50 g (0.13 mol) prepared as per example-2 in 2.5 liters of DM water was heated at 90-100° C. for 1-2 hours. Temperature of the reaction mixture was brought down to 60° C. The reaction was continued for 12 h at this temperature. Completion of the reaction was checked by HPLC. The reaction mixture was filtered through celite and the filtrate treated with 0.5 g of potassium iodide as in example-3. Carbon treatment followed by water removal produces oxaliplatin (20 g, 38percent).

Reference： [1] Patent: US2008/207935, 2008, A1, . Location in patent: Page/Page column 7

8
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
30%	With silver(l) oxide In water at 90 - 100℃; for 10 - 12 h;	Cis-diiodo-trans-l-1,2-diaminocyclohexane (40g, 0.07 mol) prepared as per example-1 was heated at 90-100° C. in 2 liters of DM water with 16.48g of silver oxide (0.07 mol) and oxalic acid dihydrate, 8.06 g (0.06 mol) for 10-12h. The reaction mixture was filtered through celite and worked up as usual to give 8.3g of oxaliplatin (30percent).

Reference： [1] Patent: WO2005/75489, 2005, A1, . Location in patent: Page/Page column 14; 24

9
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
30%	With silver(l) oxide In water at 90 - 100℃; for 10 - 12 h;	Cis-diiodo-trans-l-1,2-diaminocyclohexane (40 g, 0.07 mol) prepared as per example-1 was heated at 90-100° C. in 2 liters of DM water with 16.48 g of silver oxide (0.07 mol) and oxalic acid dihydrate, 8.06 g (0.06 mol) for 10-12 h. The reaction mixture was filtered through celite and worked up as usual to give 8.3 g of oxaliplatin (30percent).

Reference： [1] Patent: US2008/207935, 2008, A1, . Location in patent: Page/Page column 8

10
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[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
67%	at 60 - 70℃; for 5 - 6 h; Heating / reflux	A mixture of 25g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25g of silver oxide (0.065 mol) and acetic acid (7.9g, 0.13 mol) was heated at 60-70 C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC. Cis-dichloro compound was consumed in 4-5 h and the cis-diacetato compound was formed in 85-90percent (by HPLC). To the reaction was added dipotassium oxalate mono- hydrate (10.76g, 0.058mol) and heating continued with reaction monitoring. The reaction was complete in 6h. The reaction mixture was cooled to RT and filtered through celite 2-3 times to get a clear filtrate which was treated with potassium iodide to remove dissolved silver ions. Carbon treatment and water recovery produces 17.5g of oxaliplatin (67percent).; EXAMPLE-6 Cis-oxalato-trans-l-1,2-diaminocyclohexane platinum(II) (Oxaliplatin); A mixture of 25g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25g of silver oxide (0.065 mol) and acetic acid (7.9g, 0.13 mol) was heated at 60-70 C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC. Cis-dichloro compound was consumed in 4-5 h and the cis-diacetato compound was formed in 85-95percent (by HPLC). The reaction mixture was filtered through celite 2-3 times to get a clear filtrate. Water was recovered at 50 C under reduced pressure to give cis-diacetato-trans-l-diaminocyclohexane platinum(II) as a white solid (21g, 83percent). The above solid (21g, 0.049 mol) was again dissolved in water 2.1 liters and heated with dipotassium oxalate monohydrate, 8.11 g (0.044 mol) at 60-70 C for 5-6h. Workup of the reaction as in example-5 produced 17. 5g of oxaliplatin (67percent).; EXAMPLE-8 Cis-oxalato-trans-l-1,2-diaminocyclohexane platinum(II) (Oxaliplatin); Cis-diiodo-trans-l-1,2-diaminocyclohexane (50g, 0.09 mol) prepared as per example-1 was heated with stirring in 2.5 liters of DM water at 80-90 C. with acetic acid (10.66g) and silver oxide, 20.88g (0.09 mol). The reaction was complete in 4h (by HPLC). The reaction mixture was filtered through celite and the clear filtrate was treated with dipotassium oxalate monohydrate, 14.9g (0.08 mol) at 60 C. under stirring. The reaction was continued at this temperature for 5h and then subsequent work up produced 21.44g of oxaliplatin (60percent).

Reference： [1] Patent: WO2005/75489, 2005, A1, . Location in patent: Page/Page column 14; 23-24; 24-25

11
[ 61848-66-6 ]
[ 7732-18-5 ]
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
44.1%	Stage #1: at 20℃; for 48 h; Stage #2: at 20℃; for 4 h;	Example 4 (comparative); All procedures were made at room temperature in the absence of light.A mixture 3,80 g of fine powdered 97percent DACHPtCI₂ (9,7 mmol), 3,33 g 99percent AgNO₃ (19,4 mmol) and 38 ml water was intensively agitated for 48 hours. The solid fraction was then removed and the cake was properly sucked. 0,17 g potassium iodide (1 mmol) was added to the filtrate and stirred for 15 hours. Active carbon in an amount of 0,3 g was then added and the suspension was stirred for another 1 hour. The solid fraction was removed by filtration and the cake was prop- erly sucked. 1 ,23 g oxalic acid dihydrate p.a. (39,76 mmol) was added to the filtrate and the mixture was stirred for 4 hours. The solid oxaliplatin was filtered, washed four times with 2 ml iced water and six times with 5 ml of ethanol. Oxaliplatin was dried under nitrogen flow at 4O⁰C to the constant weight. The yield was 2,40 g (62,3percent based on starting DACHPtCI₂). The appearance of the product was light yellow. The content of silver was less than 0.0003 mass percent, the content of analogous hydroxo-bridged dimeric platinum complex was 0,25percent, the content of oxalic acid was 0,03percent and the total content of related impurities was 0,45percent (by HPLC method).The crude product was dissolved in 105 ml water at 95-97⁰C. The hot solution was filtered without delay, the filtrate was cooled to 5⁰C EPO <DP n="23"/>and stirred for an additional 2 hours. The final solid oxaliplatin was filtered, washed twice with 2 ml iced water and six times with 5 ml of ethanol. The oxaliplatin was dried under nitrogen flow at 4O⁰C to the constant weight. The yield was 1,70 g (44,1percent based on the starting DACHPtCI₂). The appearance of the product was white. The content of silver was less than 0.0002 mass percent, the content of analogous hy- droxo-bridged dimeric Pt-complex was 0,12percent, the content of oxalic acid was 0,02percent and the total content of related impurities was 0,21percent (by HPLC method).

Reference： [1] Patent: WO2006/108428, 2006, A1, . Location in patent: Page/Page column 21-22

12
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[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
20%	With potassium iodide; silver(l) oxide In water at 90 - 100℃; for 10 - 12 h;	A mixture of 50g of potassium tetrachloroplatinate (0.12 mol), trans-l-1,2-diamino cyclohexane, 13.74g (0.12 mol), 25.15g of silver oxide (0.10 mol) and 13.66g of oxalic acid dihydrate (0.10 mol) were heated together in 3 liters of DM water at 90-100 C for 10-12 h. The reaction mixture was cooled to 50 C. filtered through celite. The filtrate was treated with 0.5g of potassim iodide at 30 C for 10-12h in dark. Then again filtered through celite. The filtrate was treated with activated carbon to remove colour. Removal of ~2.8 liters of water at 60 C. under vacuum produces oxaliplatin as a white crystalline solid (10g, 20 percent).

Reference： [1] Patent: WO2005/75489, 2005, A1, . Location in patent: Page/Page column 14; 21-22

13
[ 61848-66-6 ]
[ 33081-83-3 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
50%	at 85 - 88℃; for 8 - 10 h;	An aqueous solution of tetrabutylammonium oxalate, prepared by dissolving oxalic acid (8.29 g, 0.0658 mol) in a 40percent solution of tetrabutylammonium hydroxide (approx. 88 mL, 0.131 mol) and adjusting the pH to 7, was added to solid dichloro((frans-E-1 ,2- diaminocyclohexane)platinum(ll)) (1Og, 0.0263 mol) followed by 1.1 L of isoamyl alcohol (3-methyl-1-butanol). In this mixture, the molar ratio of platinum(ll) compound:oxalate was 1 :2.5, the ratio of alcohohwater (v/v) 95:5, and the amount of dichloro((fra/7s~.-1 ,2- diaminocyclohexane)platinum(ll) in the solvent reaction mixture was 8.3 g/L.The mixture was stirred for 8h whilst its internal temperature was thermostatically maintained at 85°C. During this time the relatively insoluble dichloro(frans-t-1 ,2-diaminocyclohexane)platinum(ll) was replaced by white oxaliplatin which precipitated out of solution.Thereafter, the mixture was cooled at 4°C, the solids collected by suction filtration and washed with several volumes of dry acetone. The relatively <n="15"/>pure oxaliplatin was recovered with a yield of 83percent (8.71 g) as an off-white crystalline solid.Purification was effected by dissolving the above solids in 500 ml_ water preheated to 70-75⁰C. When approximately 95percent of the material was in solution, it was filtered and the liquor cooled at 4⁰C for 6-1Oh. The precipitated white crystals were collected by suction filtration, washed with several small volumes of dry acetone and dried at 50⁰C. Yield = 47percent (4.9g). (1st crop).The subsequent crop was obtained by concentrating the mother liquor under vacuum. The resulting solids had a yellow colouration due to contamination with small amounts of unreacted dichloro(frans-?-1 ,2- diaminocyclohexane)platinum(ll).The latter was removed by careful washing with minimal volumes of dmf until the yellow colour was removed. The white solids were then washed with acetone and dried at 50°C.The combined crops (1 _{2) totalled 7.47g (72percent overall yield).; Example 2; PtdachCI&2} (50 g, 0.132 mol), tetrabutylammonium oxalate (274 ml, 0.96 M) (prepared by dissolving 33.2 g oxalic acid in 0.35 L 40percent tetrabutylammonium hydroxide and evaporating 11O mL water), and isoamyl alcohol (925 ml) were charged into a reactor. In this mixture the molar ratio of PtdachCI₂:oxalate was 1 :2, the ratio alcohoLwater (v/v) was 90:10 and the amount of PtdachCI₂ in the reaction mixture was 42 g/L The mixture was heated to an internal temperature of 88 ⁰C for 8-1Oh accompanied by vigorous stirring. During this time the relatively insoluble PtdachCI₂ was replaced by white oxaliplatin which precipitated out of the reaction mixture. <n="16"/>After reaction, the mixture was cooled to an internal temperature of 2-4 ⁰C for 1-2h, whereafter the precipitate was recovered via suction filtration on a sintered glass filter. The precipitate was washed with several volumes of dry acetone and dried. A crude yield of 86percent (45 g) oxaliplatin (relative to PtdachCI₂) was obtained.Purification was effected by dissolving the crude solids in 2.5 L water at a temperature of 75 ⁰C. When approximately 95percent of the material was in solution, it was filtered and the liquor cooled at 4 ⁰C for 6-1Oh. The precipitated crystals were collected via suction filtration and washed with dry acetone. Yield = 28 g (50percent relative to PtdachCI₂).A subsequent crop was obtained by concentrating the mother liquor under vacuum at 60 ⁰C. The precipitated white solids were collected, washed with dry acetone and dried under vacuum at 60 ⁰C.The combined yield of crops was 65 percent (relative to PtdachCI₂).; Example 3; PtdachCI₂ (10 g, 0.026 mol), tetrabutylammonium oxalate (0.066 mol) (prepared by dissolving 8.3 g oxalic acid in 88 ml of a 40percent wt solution of tetrabutylammonium hydroxide and adjusting the pH to 7) and 520 ml 2- octanol were stirred together at 85 ⁰C for 10h. In this mixture the molar ratio of PtdachCI₂:oxalate was 1 :2.5, the ratio of alcohol:water (v/v) was 90:10 and the amount of PtdachCI₂ in the reaction mixture was 16 g/L.During this time the relatively insoluble PtdachCI₂ was replaced by white oxaliplatin which precipitated out of the reaction mixture. After reaction, the mixture was cooled at 4 ⁰C, the solids collected by suction filtration and washed with several volumes of dry acetone. The relatively pure oxaliplatin was recovered with a yield of 80percent (relative to PtdachCI₂) as an off-white crystalline solid. <n="17"/>Purification was effected by dissolving the above solids in 450 ml water preheated to 75 ⁰C. When approximately 95percent of the material was in solution, it was filtered and the liquor cooled at 4 ⁰C for 6-1Oh. The precipitated white crystals were collected by suction filtration, washed with several small volumes of dry acetone and dried at 50 ⁰C. Yield = 50percent (relative to PtdachCI₂).A subsequent crop was obtained by concentrating the mother liquor under vacuum at 60 ⁰C.The combined crops (1 _{2) totaled 7.3g (70percent relative to PtdachCI&2}).

Reference： [1] Patent: WO2007/85957, 2007, A1, . Location in patent: Page/Page column 13-16

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[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
67%	for 5 - 6 h; Heating / reflux	A mixture of 25 g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25 g of silver oxide (0.065 mol) and acetic acid (7.9 g, 0.13 mol) was heated at 60-70° C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC.Cis-dichloro compound was consumed in 4-5 h and the cis-diacetato compound was formed in 85-90percent (by HPLC). To the reaction was added dipotassium oxalate mono-hydrate (10.76 g, 0.058 mol) and heating continued with reaction monitoring. The reaction was complete in 6 h. The reaction mixture was cooled to RT and filtered through celite 2-3 times to get a clear filtrate which was treated with potassium iodide to remove dissolved silver ions. Carbon treatment and water recovery produces 17.5 g of oxaliplatin (67percent).; Example-6; Cis-oxalato-trans-l-1,2-diaminocyclohexane platinum(II) (Oxaliplatin); A mixture of 25 g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25 g of silver oxide (0.065 mol) and acetic acid (7.9 g, 0.13 mol) was heated at 60-70° C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC.Cis-dichloro compound was consumed in 4-5 h and the cis-diacetato compound was formed in 85-95percent (by HPLC). The reaction mixture was filtered through celite 2-3 times to get a clear filtrate. Water was recovered at 50° C. under reduced pressure to give cis-diacetato-trans-l-diaminocyclohexane platinum(II) as a white solid (21 g, 83percent). The above solid (21 g, 0.049 mol) was again dissolved in water 2.1 liters and heated with dipotassium oxalate monohydrate, 8.11 g (0.044 mol) at 60-70° C. for 5-6 h. Workup of the reaction as in example-5 produced 17.5 g of oxaliplatin (67percent).

Reference： [1] Patent: US2008/207935, 2008, A1, . Location in patent: Page/Page column 7-8

15
[ 144-62-7 ]
[ 61825-94-3 ]

Reference： [1] Patent: WO2006/108428, 2006, A1, . Location in patent: Page/Page column 17-21

16
[ 583-52-8 ]
[ 61825-94-3 ]

Reference： [1] Patent: WO2005/75489, 2005, A1, . Location in patent: Page/Page column 14; 25-26

17
[ 583-52-8 ]
[ 61825-94-3 ]

Reference： [1] Patent: US2008/207935, 2008, A1, . Location in patent: Page/Page column 8

18
[ 62-76-0 ]
[ 61825-94-3 ]

Reference： [1] Patent: US2008/319061, 2008, A1, . Location in patent: Page/Page column 4

19
[ 61848-66-6 ]
[ 61825-94-3 ]

Reference： [1] Inorganic Chemistry, [2] Inorganic Chemistry, 1988, vol. 27, p. 4106 - 4113

[ 61825-94-3 ] Synthesis Path-Downstream 1~88

1
[ 61848-66-6 ]
[ 33081-83-3 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
50 - 72%	In i-Amyl alcohol; water; at 85 - 88℃; for 8 - 10h;Product distribution / selectivity;	An aqueous solution of tetrabutylammonium oxalate, prepared by dissolving oxalic acid (8.29 g, 0.0658 mol) in a 40% solution of tetrabutylammonium hydroxide (approx. 88 mL, 0.131 mol) and adjusting the pH to 7, was added to solid dichloro((frans-E-1 ,2- diaminocyclohexane)platinum(ll)) (1Og, 0.0263 mol) followed by 1.1 L of isoamyl alcohol (3-methyl-1-butanol). In this mixture, the molar ratio of platinum(ll) compound:oxalate was 1 :2.5, the ratio of alcohohwater (v/v) 95:5, and the amount of dichloro((fra/7s~.-1 ,2- diaminocyclohexane)platinum(ll) in the solvent reaction mixture was 8.3 g/L.The mixture was stirred for 8h whilst its internal temperature was thermostatically maintained at 85C. During this time the relatively insoluble dichloro(frans-t-1 ,2-diaminocyclohexane)platinum(ll) was replaced by white oxaliplatin which precipitated out of solution.Thereafter, the mixture was cooled at 4C, the solids collected by suction filtration and washed with several volumes of dry acetone. The relatively <n="15"/>pure oxaliplatin was recovered with a yield of 83% (8.71 g) as an off-white crystalline solid.Purification was effected by dissolving the above solids in 500 ml_ water preheated to 70-750C. When approximately 95% of the material was in solution, it was filtered and the liquor cooled at 40C for 6-1Oh. The precipitated white crystals were collected by suction filtration, washed with several small volumes of dry acetone and dried at 500C. Yield = 47% (4.9g). (1st crop).The subsequent crop was obtained by concentrating the mother liquor under vacuum. The resulting solids had a yellow colouration due to contamination with small amounts of unreacted dichloro(frans-?-1 ,2- diaminocyclohexane)platinum(ll).The latter was removed by careful washing with minimal volumes of dmf until the yellow colour was removed. The white solids were then washed with acetone and dried at 50C.The combined crops (1 & 2) totalled 7.47g (72% overall yield).; Example 2; PtdachCI2 (50 g, 0.132 mol), tetrabutylammonium oxalate (274 ml, 0.96 M) (prepared by dissolving 33.2 g oxalic acid in 0.35 L 40% tetrabutylammonium hydroxide and evaporating 11O mL water), and isoamyl alcohol (925 ml) were charged into a reactor. In this mixture the molar ratio of PtdachCI2:oxalate was 1 :2, the ratio alcohoLwater (v/v) was 90:10 and the amount of PtdachCI2 in the reaction mixture was 42 g/L The mixture was heated to an internal temperature of 88 0C for 8-1Oh accompanied by vigorous stirring. During this time the relatively insoluble PtdachCI2 was replaced by white oxaliplatin which precipitated out of the reaction mixture. <n="16"/>After reaction, the mixture was cooled to an internal temperature of 2-4 0C for 1-2h, whereafter the precipitate was recovered via suction filtration on a sintered glass filter. The precipitate was washed with several volumes of dry acetone and dried. A crude yield of 86% (45 g) oxaliplatin (relative to PtdachCI2) was obtained.Purification was effected by dissolving the crude solids in 2.5 L water at a temperature of 75 0C. When approximately 95% of the material was in solution, it was filtered and the liquor cooled at 4 0C for 6-1Oh. The precipitated crystals were collected via suction filtration and washed with dry acetone. Yield = 28 g (50% relative to PtdachCI2).A subsequent crop was obtained by concentrating the mother liquor under vacuum at 60 0C. The precipitated white solids were collected, washed with dry acetone and dried under vacuum at 60 0C.The combined yield of crops was 65 % (relative to PtdachCI2).; Example 3; PtdachCI2 (10 g, 0.026 mol), tetrabutylammonium oxalate (0.066 mol) (prepared by dissolving 8.3 g oxalic acid in 88 ml of a 40% wt solution of tetrabutylammonium hydroxide and adjusting the pH to 7) and 520 ml 2- octanol were stirred together at 85 0C for 10h. In this mixture the molar ratio of PtdachCI2:oxalate was 1 :2.5, the ratio of alcohol:water (v/v) was 90:10 and the amount of PtdachCI2 in the reaction mixture was 16 g/L.During this time the relatively insoluble PtdachCI2 was replaced by white oxaliplatin which precipitated out of the reaction mixture. After reaction, the mixture was cooled at 4 0C, the solids collected by suction filtration and washed with several volumes of dry acetone. The relatively pure oxaliplatin was recovered with a yield of 80% (relative to PtdachCI2) as an off-white crystalline solid. <n="17"/>Purification was effected by dissolving the above solids in 450 ml water preheated to 75 0C. When approximately 95% of the material was in solution, it was filtered and the liquor cooled at 4 0C for 6-1Oh. The precipitated white crystals were collected by suction filtration, washed with several small volumes of dry acetone and dried at 50 0C. Yield = 50% (relative to PtdachCI2).A subsequent crop was obtained by concentrating the mother liquor under vacuum at 60 0C.The combined crops (1 & 2) totaled 7.3g (70% relative to PtdachCI2).

Reference： [1]Patent: WO2007/85957,2007,A1 .Location in patent: Page/Page column 13-16

2
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
62.9 - 70.5%		A mixture of 3,88 g of fine powdered DACHPtCI2 98% (10 mmol), 1.55 g purified Celite, 3.41 g AgNO3 99.5% (20 mmol) and 27 ml pu- rified water was intensively stirred 5 minutes at room temperature and then 2 hours at 450C. The suspension was cooled to 30C and then filtered through the plate with active charcoal. The crude acidic filtrate had the content of silver ions 0.0018 mass.% ,i.e. 18 p.p.m. 0.19 g of Smopex-101 was added to the crude filtrate and the sus- pension was stirred 1 hour at room temperature. The solid fraction was then removed by filtration. The purifying procedure with <n="16"/>Smopex-101 was repeated once again and the purified solution was then filtered through an ultrafilter with the porosity 0.22 mum. 1.27 g oxalic acid dihydrate 99.5% (10 mmol) was added to the purified solution, pH value was adjusted to 2.9 by means of 40% solution of KOH1 the mixture was stirred 4 hours at room temperature and the resulting suspension was cooled to 30C. The final solid oxaliplatin was separated by filtration, washed four times with 5 ml ice water and four times with 5 ml ethanol. Oxaliplatin was dried under nitrogen flow at 400C to the constant weight. The yield of oxaliplatin was 2.80 g (70.5% based on starting DACHPtCI2). The appearance of the product was white. The content of silver was less than 0.00005 mass %, i.e. 0.5 p.p.m., the content of oxalic acid was 0.04%, the content of platinum(ll) diaqua-complex was 0.08%, and the total content of related impurities was 0.22% (by HPLC method).; Example 2; The same procedure according to Example 1 with exception that 0.39 g Dowex 50x8 in H-cycle was used instead of 0.19 g Smopex- 101 for purifying of the crude filtrate and that time of purification was 2 hours instead of 1 hour.The yield of oxaliplatin was 2,50 g (62.9% based on startingDACHPtCI2). The appearance of the product was white. The content of silver was 0.0001 mass %, i.e. 1 p.p.m., the content of oxalic acid was 0,04%, the content of platinum(ll) diaqua-complex was 0.09%, <n="17"/>and the total content of related impurities was 0.25% (by HPLC method).; Example 3 (comparative, without Celite); The same procedure according to Example 1 with exception that no Celite was used in the procedure. The crude acidic filtrate had the content of silver ions 0.2500 mass.%, i.e. 2500 p.p.m.The yield of oxaliplatin was 2.60 g (65.5% based on starting DACHPtCI2). The appearance of the product was white. The content of silver was 0.0220 mass %, i.e. 220 p.p.m.
54%		Silver nitrate (80.6 g) is added to a suspension of 88.9 g of (SP-4-2)-dichloro-[(1R,2R)-1,2-cyclohexanediamine-N,N']platinum(II) in 900 ml of water, and the obtained mixture is stirred for 70 hours at room temperature, in the dark. The insoluble portion is filtered off of the reaction mixture, and this portion is washed with 100 ml of water. Tetraethylammonium (2,5 g) iodide is added to the filtrate mixed with the washing liquid, and the obtained mixture is stirred for 16 hours. Activated charcoal (0,6 g) is added to the reaction mixture, and the mixture is filtered. Oxalic acid dihydrate (29, 5 g) is added to the obtained filtrate under stirring, and 4 hours later the precipitated oxaliplatin is filtered off. The filter cake is washed with 30 ml of water and 500 ml of ethanol divided into five portions, and the raw product is dried in a vacuum drier. After recrystallisation from water, the separated oxaliplatin is washed with 30 ml of water and 400 ml of ethanol divided into five portions, and dried in a vacuum drier at 70 C up to a constant weight. Oxaliplatin is obtained in a yield of 50,2 g (54 % of the theoretical yield based on the starting (SP-4- 2)-dichloro-[(1R,2R)-1,2-cyclohexanediamine-N,N']platinum(II). The obtained oxaliplatin contains less than 0.001 % by weight of alkali metals, less than 0.0002 % by weight of silver, and less than 0.001 % of nitrates (NO3). The content of oxalic acid is lower than 0.01 % by weight.
40.3%		A mixture 3.88 g of fine powdered DACHPtCI2 98% (10 mmol), 3.41 g AgNO3 99.5% (20 mmol) and 27 ml purified water was intensively stirred 70 hours at room temperature. The suspension was cooled to 30C and then filtered through the plate with active charcoal. The crude acidic filtrate had the content of silver ions 0.0060 mass.% ,i.e. 60 p.p.m. 0,17 g potassium iodide (1 mmol) was added to the filtrate and stirred for additional 15 hours. Active charcoal in an amount of 0,1 g was then added, the suspension was stirred for another 1 hour and then the solid fraction was removed by filtration. The purified solution was filtered through an ultrafilter with the porosity 0.22 mum. <n="18"/>1.27 g oxalic acid dihydrate 99.5% (10 mmol) was added to the purified solution, the mixture was stirred 4 hours at room temperature and the resulting suspension was cooled to 30C. The final solid ox- aliplatin was separated by filtration, washed four times with 5 ml ice water and four times with 5 ml ethanol. Oxaliplatin was dried under nitrogen flow at 4O0C to the constant weight.The yield of oxaliplatin was 2,51 g (63.2% based on starting DACHPtCI2). The content of silver was 0.0004 mass %, i.e. 4 p.p.m.. but the appearance of the product was light yellow.The light yellow oxaliplatin was re-crystallized from hot water (1 mass part of oxaliplatin and 42 mass part of water). The hot solution was ultrafiltered, cooled to 30C, the solid product was separated by filtration and washed three times with 5 ml of ice water. The oxaliplatin was dried under nitrogen flow at 4O0C to the constant weight. The yield was 1 ,60 g (40.3% based on the starting DACHPtCI2). The appearance of the product was white. The content of silver was 0.0002 mass %, i.e. 2 p.p.m., the content of oxalic acid was 0.03%, the content of platinum(ll) diaqua-complex was 0.10%, and the total content of related impurities was 0.21% (by HPLC method).

Reference： [1]Patent: WO2007/140804,2007,A1 .Location in patent: Page/Page column 14-16
[2]Patent: WO2005/35544,2005,A1 .Location in patent: Page/Page column 6-7
[3]Patent: WO2007/140804,2007,A1 .Location in patent: Page/Page column 16-17

3
cis-diacetato-trans-l-diaminocyclohexane platinum(II) [ No CAS ]
[ 583-52-8 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
67%	In water; at 60 - 70℃; for 5 - 6h;Heating / reflux;Product distribution / selectivity;	A mixture of 25g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25g of silver oxide (0.065 mol) and acetic acid (7.9g, 0.13 mol) was heated at 60-70 C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC. Cis-dichloro compound was consumed in 4-5 h and the cis-diacetato compound was formed in 85-90% (by HPLC). To the reaction was added dipotassium oxalate mono- hydrate (10.76g, 0.058mol) and heating continued with reaction monitoring. The reaction was complete in 6h. The reaction mixture was cooled to RT and filtered through celite 2-3 times to get a clear filtrate which was treated with potassium iodide to remove dissolved silver ions. Carbon treatment and water recovery produces 17.5g of oxaliplatin (67%).; EXAMPLE-6 Cis-oxalato-trans-l-1,2-diaminocyclohexane platinum(II) (Oxaliplatin); A mixture of 25g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25g of silver oxide (0.065 mol) and acetic acid (7.9g, 0.13 mol) was heated at 60-70 C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC. Cis-dichloro compound was consumed in 4-5 h and the cis-diacetato compound was formed in 85-95% (by HPLC). The reaction mixture was filtered through celite 2-3 times to get a clear filtrate. Water was recovered at 50 C under reduced pressure to give cis-diacetato-trans-l-diaminocyclohexane platinum(II) as a white solid (21g, 83%). The above solid (21g, 0.049 mol) was again dissolved in water 2.1 liters and heated with dipotassium oxalate monohydrate, 8.11 g (0.044 mol) at 60-70 C for 5-6h. Workup of the reaction as in example-5 produced 17. 5g of oxaliplatin (67%).; EXAMPLE-8 Cis-oxalato-trans-l-1,2-diaminocyclohexane platinum(II) (Oxaliplatin); Cis-diiodo-trans-l-1,2-diaminocyclohexane (50g, 0.09 mol) prepared as per example-1 was heated with stirring in 2.5 liters of DM water at 80-90 C. with acetic acid (10.66g) and silver oxide, 20.88g (0.09 mol). The reaction was complete in 4h (by HPLC). The reaction mixture was filtered through celite and the clear filtrate was treated with dipotassium oxalate monohydrate, 14.9g (0.08 mol) at 60 C. under stirring. The reaction was continued at this temperature for 5h and then subsequent work up produced 21.44g of oxaliplatin (60%).

Reference： [1]Patent: WO2005/75489,2005,A1 .Location in patent: Page/Page column 14; 23-24; 24-25

4
cis-bis(methanesulphonato)-trans-l-1,2-diaminocyclohexane platinum(II) [ No CAS ]
[ 583-52-8 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	In water; for 6h;Heating / reflux;Product distribution / selectivity;	A mixture of 25g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15, 25g of silver oxide (0.065 mol) and methanesulphonic acid (12. 63g, 0.13 mol) was heated at 60-70 C. in 1. 25 liters of DM water and progress of the reaction monitored by HPLC. Cis-dichloro compound was consumed in 5-6 h and the cis-disulphonato compound was formed in 85-90% (by HPLC). The reaction was filtered through celite to get a clear solution to which was added dipotassium oxalate monohydrate (10.89g, 0. 06mole) and heating continued with reaction monitoring. The reaction was complete in 6h. The reaction mixture was cooled to RT and filtered through celite 2-3 times to get a clear filtrate which was treated with potassium iodide to remove dissolved silver ions. Carbon treatment and water recovery produces 18.2g of oxaliplatin (70%); EXAMPLE-11 Cis-oxalato-trans-l-1,2-diaminocyclohexane platinum(II) (Oxaliplatin); A mixture of 37.14g of cis-diiodo-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25g of silver oxide (0.065 mol) and methanesulphonic acid (12.63g, 0.13 mol) was heated at 60-70 C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC. Cis-diiodo compound was consumed in 8-10 h and the cis-disulphonato compound was formed in 75-80% (by HPLC). The reaction mixture was filtered and to the clear filtrate was added dipotassium oxalate monohydrate (10.89, 0.06mole) and heating continued with reaction monitoring. The reaction was complete in 6h. The reaction mixture was cooled to RT and filtered through celite 2-3 times to get a clear filtrate. Carbon treatment and water recovery produces 15.6g of oxaliplatin (60%).

Reference： [1]Patent: WO2005/75489,2005,A1 .Location in patent: Page/Page column 14; 25-26

5
[ 10025-99-7 ]
[ 144-62-7 ]
trans-1,2-cyclohexanediamine [ No CAS ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
20%	With potassium iodide; silver(l) oxide; In water; at 90 - 100℃; for 10 - 12h;Product distribution / selectivity;	A mixture of 50g of potassium tetrachloroplatinate (0.12 mol), trans-l-1,2-diamino cyclohexane, 13.74g (0.12 mol), 25.15g of silver oxide (0.10 mol) and 13.66g of oxalic acid dihydrate (0.10 mol) were heated together in 3 liters of DM water at 90-100 C for 10-12 h. The reaction mixture was cooled to 50 C. filtered through celite. The filtrate was treated with 0.5g of potassim iodide at 30 C for 10-12h in dark. Then again filtered through celite. The filtrate was treated with activated carbon to remove colour. Removal of ~2.8 liters of water at 60 C. under vacuum produces oxaliplatin as a white crystalline solid (10g, 20 %).

Reference： [1]Patent: WO2005/75489,2005,A1 .Location in patent: Page/Page column 14; 21-22

6
cis-diiodo-trans-l-1,2-diaminocyclohexane platinum(II) [ No CAS ]
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
30%	With silver(l) oxide; In water; at 90 - 100℃; for 10 - 12h;Product distribution / selectivity;	Cis-diiodo-trans-l-1,2-diaminocyclohexane (40g, 0.07 mol) prepared as per example-1 was heated at 90-100 C. in 2 liters of DM water with 16.48g of silver oxide (0.07 mol) and oxalic acid dihydrate, 8.06 g (0.06 mol) for 10-12h. The reaction mixture was filtered through celite and worked up as usual to give 8.3g of oxaliplatin (30%).

Reference： [1]Patent: WO2005/75489,2005,A1 .Location in patent: Page/Page column 14; 24

7
cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) [ No CAS ]
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
38%	With silver(l) oxide; In water; at 60 - 100℃; for 13 - 14h;Product distribution / selectivity;	A mixture of silver oxide (27.14g, 0.1 lmol) and oxalic acid dihydrate (14.75g, 0.1 lmol) and cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II), 50g (0. 13mol) prepared as per example-2 in 2.5liters of DM water was heated at 90-100 C. for 1-2 hours. Temperature of the reaction mixture was brought down to 60 C. The reaction was continued for 12h at this temperature. Completion of the reaction was checked by HPLC. The reaction mixture was filtered through celite and the filtrate treated with 0.5g of potassium iodide as in example-3. Carbon treatment followed by water removal produces oxaliplatin (20g, 38%).

Reference： [1]Patent: WO2005/75489,2005,A1 .Location in patent: Page/Page column 14; 22

8
potassium platinum(II) oxalate [ No CAS ]
trans-1,2-cyclohexanediamine [ No CAS ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
15%	With acetic acid; In water; at 90℃; for 6h;pH 6.6 - 7.5;Product distribution / selectivity;	K2Pt(C2O4)2.2H2O (4.50g, 9.97 mmol) was dissolved in distilled water (815ml) at 90C to provide a platinum oxalate solution. One equivalent of optically pure trans-l-1,2-diaminocyclohexane (produced by a method as described in Hans-Jorg Schanz, Michael A. Linseis and Declan G. Gilheany, Improved resolution methods for (R,R)- and (S,S)-cyclohexane-1,2-diamine and (R)-and (S)-Binol. Tetrahedron Asymmetry 12 (2003), 2763-2769) (1.06g, 9. 27mmol) was dissolved in distilled water (74ml) and the pH adjusted with dilute acetic acid to between 6.6-7. 5, to provide an amine solution. The amine solution was added incrementally in eight equal portions every 45 minutes to the platinum oxalate solution over 6 hours where after the solution was cooled to room temperature and the precipitate filtered. The solvent was removed from the filtrate under vacuum. The solid obtained from the filtrate contains oxaliplatin in a crude form. This solid was suspended in distilled water (40ml) over a water bath at 70C for a period of time (10 minutes) where after the remaining solid was removed by filtration. The filtrate was cooled and 0.75 molar equivalents of Cs2C2O4 in relation to K2Pt(C2O4)2.2H2O was added. The solution was stirred for approximately 20 minutes and the precipitate which formed was filtered. The solvent was subsequently vacuum evaporated. The remaining solid was suspended in a small portion of distilled water (6ml) and heated to 70C for a period of time (10 minutes) and filtered to provide a filtrate (A). The solid which did not dissolve contained mostly oxaliplatin with a small portion of oxalate salt (see Figure 3). This was readily purified by washing the solid with a small portion (3ml) of distilled water to obtain pure oxaliplatin (see Figure 4). The filtrate (A) was cooled to 5C and the precipitate filtered. The solvent was vacuum evaporated. The solid which remained contained mainly oxaliplatin and cesium and potassium oxalates. The oxalate salts were readily removed by washing 5 times with small portions of distilled water (3ml) resulting in a further amount of pure oxaliplatin. All the oxaliplatin samples produced had a chemical purity >99.5% (see Figure 4) and optical purity of >99.98% (see Figure 5). The overall yield of chemically and optically pure oxaliplatin was 15%.
15%	In water; acetone; at 95℃; for 1.5h;Product distribution / selectivity;	Both K2PtCl4 (41.5g ; 92.0 mmole) and 271.17g (1178.8 mmole) of K2C2O4 were simultaneously dissolved in 600ml water and kept at 95C for at least 1 hour, during which time K2Pt(C2O4)2.2H2O gradually precipitated. The solution was cooled for over 2 hours at 5C, filtered and washed with 5 80 ml portions of water and finally with acetone. After 45 minutes in an oven at 50C pure dry K2Pt(C2O4)2.2H2O (43.72g ; 89.96 mmole) was obtained. The product was dissolved in 120ml pure water at 95C and trans-l-1,2-diaminocyclohexane (10.28g ; 90.03 mmole) dissolved in 40moi acetone was added and stirred for 1 1/2 hours at 95C. It was left to stand at room temperature for over 2 hours, The solvent was removed from the filtrate under vacuum. The solid obtained from the filtrate contained most of the oxaliplatin in a crude form. This solid was suspended in distilled water (388ml) over a water bath at 70C for a period of time (20 minutes) where after the remaining solid was removed by filtration. The filtrate was cooled and 0.75 molar equivalents of Cs2C2O4 in relation to K2Pt(C2O4)2.2H2O was added. The solution was stirred for approximately 20 minutes and the precipitate which formed was filtered. The solvent was subsequently vacuum evaporated. The remaining solid was suspended in a portion of distilled water (58ml) and heated at 70C for a period of time (20 minutes) and filtered to provide a filtrate (A). The solid which did not dissolve contained mostly oxaliplatin with a portion of oxalate salt. This was readily purified by washing the solid with a portion (29mut) of distilled water to obtain pure oxaliplatin. The filtrate (A) was cooled to 5C and the precipitate filtered. The solvent was vacuum evaporated. The solid which remained contained mainly oxaliplatin and cesium and potassium oxalates. The oxalate salts were readily removed by washing 5 times with portions of distilled water (29ml) resulting in pure oxaliplatin. All the oxaliplatin samples produced had a chemical purity >99.5% and optical purity of >99.98%. The overall yield of chemically and optically pure oxaliplatin was 15%.

Reference： [1]Patent: WO2005/51966,2005,A1 .Location in patent: Page/Page column 17-18
[2]Patent: WO2005/51966,2005,A1 .Location in patent: Page/Page column 18-19

9
C₆H₁₈N₂O₂Pt⁽²⁺⁾*2NO₃^(1-) [ No CAS ]
[ 1113-38-8 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	In water; at 45℃; for 8h;	K2[PtCl4] (59.60g) is dissolved in water (439 ml). Potassium iodide (168.0 g) is dissolved in water (147 ml). Both solutions are purified and stirred for 30 min. Trans-I-1,2-diaminocyclohexane (18.39 g) is dissolved in water (72 ml.) The solution is added to the platinum-containing solution while stirring and the agitation is continued for 72 hours. The obtained suspension is filtered. The filtered deposit is washed with water six times (200 ml) and subsequently dried. Yield of 1,2-diamonocyclohexane-diiodoplatinum II: 77.9 g (96%). The obtained Trans-1-1,2 diaminocyclohexane-diiodo-platinum(II) is suspended in water (1389 ml) and the suspension is heated at 45 degrees C. Silver nitrate (43.91 g) is dissolved in water (139 ml) and this solution is purified with platinum-containing solution. The resulting mixture is agitated for 8 hours at 45 degrees C. The suspension is subsequently cooled within 6 hours at 6 degrees C. and filtered. Di-<strong>[1113-38-8]ammonium oxalate</strong> monohydrate (20.19 g) is dissolved in water (278 mL). Water (3333 mL), <strong>[1113-38-8]ammonium oxalate</strong> solution and platinum-containing solution are purified and agitated for 8 hours at 45 degrees C. Subsequently activated carbon is added (3.05 g) and again further agitated for 16 hours. It is filtered and the active carbon treatment is repeated. The obtained solution is then led through a sterile filter into a rotary evaporator and concentrated at 55 to 65 degrees C. in a vacuum to about 110 ml. The obtained suspension is filtered and the deposit is agitated thrice in water (28 ml) for 10 min. Subsequently it is washed thrice with methanol (139 ml). The filtered deposit is dried in sterile air stream for at least 24 hours. Yield of oxalato (trans-1-1,2-diaminocyclohexane) platinum (II): 33.88 g (80%).

Reference： [1]Patent: US2005/197389,2005,A1 .Location in patent: Page/Page column 2; 3

10
2CH₃O₃S^(1-)*C₆H₁₈N₂O₂Pt⁽²⁺⁾ [ No CAS ]
[ 61825-94-3 ]

Reference： [1]Patent: WO2005/75489,2005,A1 .Location in patent: Page/Page column 18

11
[Pt(OH)2(trans-(1R,2R)-diaminocyclohexane)] [ No CAS ]
[ 144-62-7 ]
[ 61825-94-3 ]
C₁₂H₂₈N₄O₂Pt₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; at 20℃; for 4h;Product distribution / selectivity;	Example 1; All procedures were carried out at room temperature in the absence of light. A mixture of 3,80 g of fine powdered 97% DACHPtCI2 (9,7 mmol), 3,33 g 99% AgNtheta3 (19,4 mmol) and 38 ml water was intensively agitated for 48 hours. The solid fraction was then removed and a cake was properly sucked. 0,1 N solution of NaOH was added to the filtrate to adjust the pH to 12. Active carbon in an amount 0,3 g was added to the mixture and stirred for 1 hour. The solid fraction was removed by filtration and a cake was properly sucked. The yellow crude alkaline filtrate has the content of Ag+ 0,0022 mass.%, i.e. 22 ppm. 0,08 g of sodium oxalate (0,6 mmol), 0,3 g of active carbon and 0,3 g of silica gel were then added to this filtrate, pH was adjusted to 12 again and mixture was stirred 4 hours. The solid fraction was removed by filtration and a cake was properly sucked. The near colorless filtrate has the content of Ag+ 0,2 ppm. The purification process EPO <DP n="19"/>with sodium oxalate, active carbon and silica gel was repeated one times. The clear colorless filtrate has the content of Ag+ under a detection limit. 1 ,1 g oxalic acid dihydrate p.a. (8,7 mmol) was added to the filtrate and the mixture was stirred for 4 hours. The final solid ox- aliplatin was filtered, washed four times with 2 ml iced water and six times with 5 ml ethanol. Waste water was collected. Oxaliplatin was dried under nitrogen flow at 4O0C to the constant weight.The yield of oxaliplatin was 2,80 g (72,7% based on starting DACHPtCI2). The appearance of the product was white. The content of silver was less than 0.0001 mass %, the content of analogous hy- droxo-bridged dimeric platinum complex III was 0,06%, the content of oxalic acid was 0,08% and the total content of related impurities was 0,22% (by HPLC method).3 ml of concentrated hydrochloric acid was added to the waste water from oxaliplatin filtration and washing. 0,4 g of starting DACHPtCI2 with the purity greater than 98% was recovered.; Example 1All procedures were carried out at room temperature in the absence of light. A mixture of 3,80 g of fine powdered 97% DACHPtCI2 (9,7 mmol), 3,33 g 99% AgNtheta3 (19,4 mmol) and 38 ml water was intensively agitated for 48 hours. The solid fraction was then removed and a cake was properly sucked. 0,1 N solution of NaOH was added to the filtrate to adjust the pH to 12. Active carbon in an amount 0,3 g was added to the mixture and stirred for 1 hour. The solid fraction was removed by filtration and a cake was properly sucked. The yellow crude alkaline filtrate has the content of Ag+ 0,0022 mass.%, i.e. 22 ppm. 0,08 g of sodium oxalate (0,6 mmol), 0,3 g of active carbon and 0,3 g of silica gel were then added to this filtrate, pH was adjusted to 12 again and mixture was stirred 4 hours. The solid fraction was removed by filtration and a cake was properly sucked. The near colorless filtrate has the content of Ag+ 0,2 ppm. The purification process EPO <DP n="19"/>with sodium oxalate, active carbon and silica gel was repeated one times. The clear colorless filtrate has the content of Ag+ under a detection limit. 1 ,1 g oxalic acid dihydrate p.a. (8,7 mmol) was added to the filtrate and the mixture was stirred for 4 hours. The final solid ox- aliplatin was filtered, washed four times with 2 ml iced water and six times with 5 ml ethanol. Waste water was collected. Oxaliplatin was dried under nitrogen flow at 4O0C to the constant weight.The yield of oxaliplatin was 2,80 g (72,7% based on starting DACHPtCI2). The appearance of the product was white. The content of silver was less than 0.0001 mass %, the content of analogous hy- droxo-bridged dimeric platinum complex III was 0,06%, the content of oxalic acid was 0,08% and the total content of related impurities was 0,22% (by HPLC method).3 ml of concentrated hydrochloric acid was added to the waste water from oxaliplatin filtration and washing. 0,4 g of starting DACHPtCI2 with the purity greater than 98% was recovered.; Example 2; All procedures were carried out at room temperature in the absence of light.A mixture of 3,80 g of fine powdered 97% DACHPtCI2 (9,7 mmol), 3,33 g 99% AgNO3 (19,4 mmol) and 38 ml water was intensively agitated for 48 hours. The solid fraction was then removed and a cake EPO <DP n="20"/>was properly sucked. 0,1 N solution of NaOH was added to the filtrate to adjust the pH to 12. Active carbon in an amount 0,3 g was added to the mixture and stirred for 1 hour. The solid fraction was removed by filtration and a cake was properly sucked. The yellow crude alka- line filtrate has the content of Ag+ 0,0025 mass.%, i.e. 25 ppm. 0,3 g of active carbon and 0,3 g of silica gel were then added to this filtrate, the pH was adjusted to 12 again and the mixture was stirred 2 hours. The solid fraction was removed by filtration and a cake was properly sucked. The near colorless filtrate has the content of Ag+ 2 ppm. The purification process with active carbon and silica gel was repeated o...

Reference： [1]Patent: WO2006/108428,2006,A1 .Location in patent: Page/Page column 17-21

12
[ 61848-66-6 ]
[ 61825-94-3 ]

Reference： [1]Inorganic Chemistry,1988,vol. 27,p. 4106 - 4113

13
platinum(IV)Cl₂ oxalate (1R, 2R-cyclohexandiamine) [ No CAS ]
[ 61825-94-3 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1987,vol. 106,p. 381 - 381
[2]Recueil des Travaux Chimiques des Pays-Bas,1987,vol. 106,p. 381 - 381

14
[ 61825-94-3 ]
[ 27025-41-8 ]
[(μ-glutathionate)bis((1R,2R)-1,2-diaminocyclohexane)diplatinum(II)] [ No CAS ]
[bis(μ-glutathionate)bis((1R,2R)-1,2-diaminocyclohexane)diplatinum(II)] [ No CAS ]

Reference： [1]European Journal of Inorganic Chemistry,2003,p. 1206 - 1214

15
[ 61825-94-3 ]
[ 70-18-8 ]
[(μ-glutathionate)bis((1R,2R)-1,2-diaminocyclohexane)diplatinum(II)] [ No CAS ]
[bis(μ-glutathionate)bis((1R,2R)-1,2-diaminocyclohexane)diplatinum(II)] [ No CAS ]

Reference： [1]European Journal of Inorganic Chemistry,2003,p. 1206 - 1214

16
[Pt(OH)2(trans-(1R,2R)-diaminocyclohexane)] [ No CAS ]
[ 62-76-0 ]
[ 61825-94-3 ]
C₁₂H₂₈N₄O₂Pt₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 20℃; for 2 - 4h;pH 12;Absence of light;Product distribution / selectivity;	Example 1All procedures were carried out at room temperature in the absence of light.A mixture of 3.80 g of fine powdered 97% DACHPtCl2 (9.7 mmol), 3.33 g 99% AgNO3 (19.4 mmol) and 38 ml water was intensively agitated for 48 hours. The solid fraction was then removed and a cake was properly sucked. 0.1N solution of NaOH was added to the filtrate to adjust the pH to 12. Active carbon in an amount 0.3 g was added to the mixture and stirred for 1 hour. The solid fraction was removed by filtration and a cake was properly sucked. The yellow crude alkaline filtrate has the content of Ag+ 0.0022 mass. %, i.e. 22 ppm. 0.08 g of sodium oxalate (0.6 mmol), 0.3 g of active carbon and 0.3 g of silica gel were then added to this filtrate, pH was adjusted to 12 again and mixture was stirred 4 hours. The solid fraction was removed by filtration and a cake was properly sucked. The near colorless filtrate has the content of Ag+ 0.2 ppm. The purification process with sodium oxalate, active carbon and silica gel was repeated one times. The clear colorless filtrate has the content of Ag+ under a detection limit. 1.1 g oxalic acid dihydrate p.a. (8.7 mmol) was added to the filtrate and the mixture was stirred for 4 hours. The final solid oxaliplatin was filtered, washed four times with 2 ml iced water and six times with 5 ml ethanol. Waste water was collected. Oxaliplatin was dried under nitrogen flow at 40 C. to the constant weight.The yield of oxaliplatin was 2.80 g (72.7% based on starting DACHPtCl2). The appearance of the product was white. The content of silver was less than 0.0001 mass %, the content of analogous hydroxo-bridged dimeric platinum complex III was 0.06%, the content of oxalic acid was 0.08% and the total content of related impurities was 0.22% (by HPLC method).3 ml of concentrated hydrochloric acid was added to the waste water from oxaliplatin filtration and washing. 0.4 g of starting DACHPtCl2 with the purity greater than 98% was recovered.Example 2All procedures were carried out at room temperature in the absence of light.A mixture of 3.80 g of fine powdered 97% DACHPtCl2 (9.7 mmol), 3.33 g 99% AgNO3 (19.4 mmol) and 38 ml water was intensively agitated for 48 hours. The solid fraction was then removed and a cake was properly sucked. 0.1N solution of NaOH was added to the filtrate to adjust the pH to 12. Active carbon in an amount 0.3 g was added to the mixture and stirred for 1 hour. The solid fraction was removed by filtration and a cake was properly sucked. The yellow crude alkaline filtrate has the content of Ag+ 0.0025 mass. %, i.e. 25 ppm. 0.3 g of active carbon and 0.3 g of silica gel were then added to this filtrate, the pH was adjusted to 12 again and the mixture was stirred 2 hours. The solid fraction was removed by filtration and a cake was properly sucked. The near colorless filtrate has the content of Ag+ 2 ppm. The purification process with active carbon and silica gel was repeated one times. The clear colorless filtrate has the content of Ag+ 0.3 ppm. The purification process with active carbon and silica gel was repeated one times. The clear colorless filtrate has the content of Ag+ under a detection limit. 1.23 g oxalic acid dihydrate p.a. (9.76 mmol) was added to the filtrate and the mixture was stirred for 4 hours. The final solid oxaliplatin was filtered, washed four times with 2 ml iced water and six times with 5 ml ethanol. Oxaliplatin was dried under nitrogen flow at 40 C. to the constant weight.The yield of oxaliplatin was 2.68 g (69.5% based on starting DACHPtCl2). The appearance of the product was white. The content of silver was less than 0.0003 mass %, the content of analogous hydroxo-bridged dimeric platinum complex III was 0.03%, the content of oxalic acid was 0.06% and the total content of related impurities was 0.18% (by HPLC method).

Reference： [1]Patent: US2008/319061,2008,A1 .Location in patent: Page/Page column 4

17
[Pt(OH)2(trans-(1R,2R)-diaminocyclohexane)] [ No CAS ]
[ 61825-94-3 ]
C₁₂H₂₈N₄O₂Pt₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With oxalic acid; In water; for 4h;Product distribution / selectivity;	Example 3All procedures were carried out at room temperature in the absence of light.A mixture of 3.80 g of fine powdered 97% DACHPtCl2 (9.7 mmol), 3.33 g 99% AgNO3 (19.4 mmol) and 38 ml water was intensively agitated for 48 hours. The solid fraction was then removed and a cake was properly sucked. 0.1 N solution of NaOH was added to the filtrate to adjust the pH to 12. Active carbon in an amount 0.3 g was added to the mixture and stirred for 1 hour. The solid fraction was removed by filtration and a cake was properly sucked. The yellow crude alkaline filtrate has the content of Ag+ 25 ppm. The filtrate was poured on a column with 30 ml of wet DOWEX 50W-X8 (Na+ cycle) (54 meqv.) and the eluent including necessary amount of washing water was carefully collected and partially concentrated. 0.3 g of active carbon and 0.3 g of silica gel were then added to the concentrated eluent, the pH was adjusted to 12 again and the mixture was stirred for 2 hours. The solid fraction was removed by filtration and a cake was properly sucked. The resulting filtrate was colorless and it has the content of Ag+ 0.03 ppm. 1.23 g oxalic acid dihydrate p.a. (9.76 mmol) was added to the filtrate and the mixture was stirred for 4 hours. The final solid oxaliplatin was filtered, washed four times with 2 ml iced water and six times with 5 ml ethanol. Oxaliplatin was dried under nitrogen flow at 40 C. to the constant weight. The yield was 2.50 g (164.9% based on starting DACHPtCl2). The appearance of the product was white. The content of silver was less than 0.0003 mass %, the content of hydroxo-bridged dimeric platinum complex III was 0.04%, the content of oxalic acid was 0.05% and the total content of related impurities was 0.24% (by HPLC method).Example 4 (Comparative)All procedures were made at room temperature in the absence of light.A mixture 3.80 g of fine powdered 97% DACHPtCl2 (9.7 mmol), 3.33 g 99% AgNO3 (19.4 mmol) and 38 ml water was intensively agitated for 48 hours. The solid fraction was then removed and the cake was properly sucked. 0.17 g potassium iodide (1 mmol) was added to the filtrate and stirred for 15 hours. Active carbon in an amount of 0.3 g was then added and the suspension was stirred for another 1 hour. The solid fraction was removed by filtration and the cake was properly sucked. 1.23 g oxalic acid dihydrate p.a. (39.76 mmol) was added to the filtrate and the mixture was stirred for 4 hours. The solid oxaliplatin was filtered, washed four times with 2 ml iced water and six times with 5 ml of ethanol. Oxaliplatin was dried under nitrogen flow at 40 C. to the constant weight. The yield was 2.40 g (62.3% based on starting DACHPtCl2). The appearance of the product was light yellow. The content of silver was less than 0.0003 mass %, the content of analogous hydroxo-bridged dimeric platinum complex was 0.25%, the content of oxalic acid was 0.03% and the total content of related impurities was 0.45% (by HPLC method).The crude product was dissolved in 105 ml water at 95-97 C. The hot solution was filtered without delay, the filtrate was cooled to 5 C. and stirred for an additional 2 hours. The final solid oxaliplatin was filtered, washed twice with 2 ml iced water and six times with 5 ml of ethanol. The oxaliplatin was dried under nitrogen flow at 40 C. to the constant weight. The yield was 1.70 g (44.1% based on the starting DACHPtCl2). The appearance of the product was white. The content of silver was less than 0.0002 mass %, the content of analogous hydroxo-bridged dimeric Pt-complex was 0.12%, the content of oxalic acid was 0.02% and the total content of related impurities was 0.21% (by HPLC method).

Reference： [1]Patent: US2008/319061,2008,A1 .Location in patent: Page/Page column 5

18
trans-(R,R)-(1,2-diaminocyclohexane)diiodoplatinum(II) [ No CAS ]
[ 583-52-8 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
60%		Cis-diiodo-trans-l-1,2-diaminocyclohexane (50 g, 0.09 mol) prepared as per example-1 was heated with stirring in 2.5 liters of DM water at 80-90 C. with acetic acid (10.66 g) and silver oxide, 20.88 g (0.09 mol). The reaction was complete in 4 h (by HPLC). The reaction mixture was filtered through celite and the clear filtrate was treated with dipotassium oxalate monohydrate, 14.9 g (0.08 mmol) at 60 C. under stirring.The reaction was continued at this temperature for 5 h and then subsequent work up produced 21.44 g of oxaliplatin (60%).

Reference： [1]Patent: US2008/207935,2008,A1 .Location in patent: Page/Page column 8

19
cis-diacetato-trans-l-1,2-diaminocyclohexane platinum(II) [ No CAS ]
[ 583-52-8 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
67%	In water; for 5 - 6h;Heating / reflux;Product distribution / selectivity;	A mixture of 25 g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25 g of silver oxide (0.065 mol) and acetic acid (7.9 g, 0.13 mol) was heated at 60-70 C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC.Cis-dichloro compound was consumed in 4-5 h and the cis-diacetato compound was formed in 85-90% (by HPLC). To the reaction was added dipotassium oxalate mono-hydrate (10.76 g, 0.058 mol) and heating continued with reaction monitoring. The reaction was complete in 6 h. The reaction mixture was cooled to RT and filtered through celite 2-3 times to get a clear filtrate which was treated with potassium iodide to remove dissolved silver ions. Carbon treatment and water recovery produces 17.5 g of oxaliplatin (67%).; Example-6; Cis-oxalato-trans-l-1,2-diaminocyclohexane platinum(II) (Oxaliplatin); A mixture of 25 g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25 g of silver oxide (0.065 mol) and acetic acid (7.9 g, 0.13 mol) was heated at 60-70 C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC.Cis-dichloro compound was consumed in 4-5 h and the cis-diacetato compound was formed in 85-95% (by HPLC). The reaction mixture was filtered through celite 2-3 times to get a clear filtrate. Water was recovered at 50 C. under reduced pressure to give cis-diacetato-trans-l-diaminocyclohexane platinum(II) as a white solid (21 g, 83%). The above solid (21 g, 0.049 mol) was again dissolved in water 2.1 liters and heated with dipotassium oxalate monohydrate, 8.11 g (0.044 mol) at 60-70 C. for 5-6 h. Workup of the reaction as in example-5 produced 17.5 g of oxaliplatin (67%).

Reference： [1]Patent: US2008/207935,2008,A1 .Location in patent: Page/Page column 7-8

20
cis-bismethanesulphonato-trans-l-1,2-diaminocyclohexane platinum(II) [ No CAS ]
[ 583-52-8 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	In water; for 6h;Heating / reflux;Product distribution / selectivity;	A mixture of 25 g of cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25 g of silver oxide (0.065 mol) and methanesulphonic acid (12.63 g, 0.13 mol) was heated at 60-70 C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC.Cis-dichloro compound was consumed in 5-6 h and the cis-disulphonato compound was formed in 85-90% (by HPLC). The reaction was filtered through celite to get a clear solution to which was added dipotassium oxalate monohydrate (10.89 g, 0.06 mole) and heating continued with reaction monitoring. The reaction was complete in 6 h.The reaction mixture was cooled to RT and filtered through celite 2-3 times to get a clear filtrate which was treated with potassium iodide to remove dissolved silver ions. Carbon treatment and water recovery produces 18.2 g of oxaliplatin (70%).; Example-11; Cis-oxalato-trans-l-1,2-diaminocyclohexane platinum(II) (Oxaliplatin); A mixture of 37.14 g of cis-diiodo-trans-l-1,2-diaminocyclohexane platinum(II) (0.065 mol), 15.25 g of silver oxide (0.065 mol) and methanesulphonic acid (12.63 g, 0.13 mol) was heated at 60-70 C. in 1.25 liters of DM water and progress of the reaction monitored by HPLC.Cis-diiodo compound was consumed in 8-10 h and the cis-disulphonato compound was formed in 75-80% (by HPLC). The reaction mixture was filtered and to the clear filtrate was added dipotassium oxalate monohydrate (10.89, 0.06 mole) and heating continued with reaction monitoring. The reaction was complete in 6 h.The reaction mixture was cooled to RT and filtered through celite 2-3 times to get a clear filtrate. Carbon treatment and water recovery produces 15.6 g of oxaliplatin (60%).

Reference： [1]Patent: US2008/207935,2008,A1 .Location in patent: Page/Page column 8

21
[ 10025-99-7 ]
[ 20439-47-8 ]
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
20%	With silver(l) oxide; In water; at 90 - 100℃; for 10 - 12h;	A mixture of 50 g of potassium tetrachloroplatinate (0.12 mol), trans-l-1,2-diamino cyclohexane, 13.74 g (0.12 mol), 25.15 g of silver oxide (0.10 mol) and 13.66 g of oxalic acid dihydrate (0.10 mol) were heated together in 3 liters of DM water at 90-100 C. for 10-12 h. The reaction mixture was cooled to 50 C. filtered through celite. The filtrate was treated with 0.5 g of potassium iodide at 30 C. for 10-12 h in dark. Then again filtered through celite. The filtrate was treated with activated carbon to remove colour. Removal of 2.8 liters of water at 60 C. under vacuum produces oxaliplatin as a white crystalline solid (10 g, 20%).

Reference： [1]Patent: US2008/207935,2008,A1 .Location in patent: Page/Page column 7

22
trans-(R,R)-(1,2-diaminocyclohexane)diiodoplatinum(II) [ No CAS ]
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
30%	With silver(l) oxide; In water; at 90 - 100℃; for 10 - 12h;Product distribution / selectivity;	Cis-diiodo-trans-l-1,2-diaminocyclohexane (40 g, 0.07 mol) prepared as per example-1 was heated at 90-100 C. in 2 liters of DM water with 16.48 g of silver oxide (0.07 mol) and oxalic acid dihydrate, 8.06 g (0.06 mol) for 10-12 h. The reaction mixture was filtered through celite and worked up as usual to give 8.3 g of oxaliplatin (30%).

Reference： [1]Patent: US2008/207935,2008,A1 .Location in patent: Page/Page column 8

23
[ 61848-66-6 ]
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
38%	With silver(l) oxide; In water; at 60 - 100℃; for 13 - 14h;Product distribution / selectivity;	A mixture of silver oxide (27.14 g, 0.11 mol) and oxalic acid dihydrate (14.75 g, 0.11 mol) and cis-dichloro-trans-l-1,2-diaminocyclohexane platinum(II), 50 g (0.13 mol) prepared as per example-2 in 2.5 liters of DM water was heated at 90-100 C. for 1-2 hours. Temperature of the reaction mixture was brought down to 60 C. The reaction was continued for 12 h at this temperature. Completion of the reaction was checked by HPLC. The reaction mixture was filtered through celite and the filtrate treated with 0.5 g of potassium iodide as in example-3. Carbon treatment followed by water removal produces oxaliplatin (20 g, 38%).

Reference： [1]Patent: US2008/207935,2008,A1 .Location in patent: Page/Page column 7

24
[ 61825-94-3 ]
[ 10102-44-0 ]
[ 7647-15-6 ]
(trans-l-1,2-diaminocyclohexane)oxalatobromonitroplatinum(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	In water; acetone; at 20℃; for 18.7833h;	0.815 g (2.05 mmol) of <strong>[61825-94-3]oxaliplatin</strong> (*ra/w-(lR,2R)-(-)-l,2- Diamr?inocyclohexane-oxalatoplatiniotaiotam(II)) was suspended in 15 mL distilled water and 36 mL acetone (30:70; wateracetone mixture). 1 molar equivalent (0.211 g; 2.05 mmol) sodium bromide was dissolved in a portion of the aforementioned 15 mL distilled water and added to the aforementioned mixture. A milky white suspension was formed and immediately reacted at room temperature with NO2 gas. The reaction continued for 37 min, upon which a light green solution was obtained and the supply OfNO2 gas terminated, the reaction vessel was covered with foil and allowed to stir overnight at room temperature. After 18 h, a lime green suspension was present. Air was bubbled through this reaction mixture until the original volume was reduced to 25%. The resulting greenish-yellow precipitate was filtered, washed with 3 small aliquots of distilled water and finally dried overnight at 50 0C. Yield: 74%, Purity: 93%. Further purification of the final product can be obtained through recrystallization from hot acetone. ESI-MS: 521.7 [M+H]+ Product purity verified by hplc on a Phenomenx Curosil PFP column (250 x 4.6 mm 5 mum); 1.0 ml/min; 2.5% acetonitrile, UV 210.

Reference： [1]Patent: WO2008/155727,2008,A1 .Location in patent: Page/Page column 41-42

25
[ 61825-94-3 ]
[ 10102-44-0 ]
[ 7647-14-5 ]
(trans-l-1,2-diaminocyclohexane)oxalatochloronitroplatinum(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In water; acetone; at 20℃; for 11.25h;	Oxaliplatin (3.24 g) was suspended in a mixture of water (60 mL), containing 1 mole equivalent sodium chloride (0.47 g), and acetone (140 mL) (water: acetone 30:70). Nitrogen dioxide gas was bubbled at a moderate rate through the mixture at room temperature using a source of NO2. Dissolution of <strong>[61825-94-3]oxaliplatin</strong> occurred from the onset of NO2 addition and was accompanied by a blue-green colouration of the resulting solution. The introduction OfNO2 was discontinued after 75 minutes and the solution left to stir for 10 hr at room temperature where after it assumed a bright yellow colouration. Following evaporation of 75% of the solvent, a yellow solid precipitated. This was washed with three small aliquots of cold water and dried at 60 0C. A 75% yield of 95% (verified by hplc) pure product was obtained. Its aqueous solubility is in excess of 20 mg per mL of water from which it can be recrystallized to obtain a higher degree of purity. The solid complex is stable up to 210 0C. ESI-MS: 496.8 [M+NH4]+, 479.9 [M+H]+, 477.9 [M-H]". Product purity verified by hplc on a Phenomenx Curosil PFP column (250 x 4.6 mm 5 mum); 1.0 ml/min; 2.5% acetonitrile, UV 210. A crystallographic structure of the dihydrate of (ralphanj'-?-l,2-diaminocyclohexane)oxalatochloronitro-platinum(IV) is shown in Figure 1.

Reference： [1]Patent: WO2008/155727,2008,A1 .Location in patent: Page/Page column 41

26
[ 61848-66-6 ]
[ 7732-18-5 ]
[ 144-62-7 ]
[ 61825-94-3 ]
C₁₂H₂₈N₄O₂Pt₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44.1%		Example 4 (comparative); All procedures were made at room temperature in the absence of light.A mixture 3,80 g of fine powdered 97% DACHPtCI2 (9,7 mmol), 3,33 g 99% AgNO3 (19,4 mmol) and 38 ml water was intensively agitated for 48 hours. The solid fraction was then removed and the cake was properly sucked. 0,17 g potassium iodide (1 mmol) was added to the filtrate and stirred for 15 hours. Active carbon in an amount of 0,3 g was then added and the suspension was stirred for another 1 hour. The solid fraction was removed by filtration and the cake was prop- erly sucked. 1 ,23 g oxalic acid dihydrate p.a. (39,76 mmol) was added to the filtrate and the mixture was stirred for 4 hours. The solid oxaliplatin was filtered, washed four times with 2 ml iced water and six times with 5 ml of ethanol. Oxaliplatin was dried under nitrogen flow at 4O0C to the constant weight. The yield was 2,40 g (62,3% based on starting DACHPtCI2). The appearance of the product was light yellow. The content of silver was less than 0.0003 mass %, the content of analogous hydroxo-bridged dimeric platinum complex was 0,25%, the content of oxalic acid was 0,03% and the total content of related impurities was 0,45% (by HPLC method).The crude product was dissolved in 105 ml water at 95-970C. The hot solution was filtered without delay, the filtrate was cooled to 50C EPO <DP n="23"/>and stirred for an additional 2 hours. The final solid oxaliplatin was filtered, washed twice with 2 ml iced water and six times with 5 ml of ethanol. The oxaliplatin was dried under nitrogen flow at 4O0C to the constant weight. The yield was 1,70 g (44,1% based on the starting DACHPtCI2). The appearance of the product was white. The content of silver was less than 0.0002 mass %, the content of analogous hy- droxo-bridged dimeric Pt-complex was 0,12%, the content of oxalic acid was 0,02% and the total content of related impurities was 0,21% (by HPLC method).

Reference： [1]Patent: WO2006/108428,2006,A1 .Location in patent: Page/Page column 21-22

27
[ 61825-94-3 ]
[ 7722-84-1 ]
[ 64-19-7 ]
(OC-6-44)-acetato[(1R,2R)-cyclohexane-1,2-diamine]hydroxidooxalatoplatinum(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; at 20℃; for 19h;Darkness;	0.135 ml of 30% aqueous hydrogen peroxide was added to a liquid obtained by suspending l-OHP (200 mg) in 9 ml of acetic acid, and the mixture was stirred for 19 hours at room temperature in the dark. After completion of the reaction, the mixture was concentrated under reduced pressure several times while water was added to the system, and a solid was obtained. The solid thus obtained was recrystallized from ethanol/methanol, and thereby, the title compound (55 mg) was obtained. H-NMR (D2O): delta2.78-2.73 (2H, m), 2.17 (2H, d, J=9.2 Hz), 1.94 (3H, s), 1.54-1.44 (4H, m), 1.20-1.05 (2H, m), purity (HPLC, analysis conditions 1): 94.0%.

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 1672 - 1676
[2]Patent: US2018/250332,2018,A1 .Location in patent: Paragraph 0189

28
[ 61825-94-3 ]
[ 7722-84-1 ]
[ 64-19-7 ]
[(1R,2R)-cyclohexane-1,2-diamine-N,N']hexanoatohydroxidooxalatoplatinum(IV) [ No CAS ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 1672 - 1676

29
[ 61825-94-3 ]
[ 79-08-3 ]
di-2-bromoacetato[(1R,2R)-cyclohexane-1,2-diamine-N,N']oxalatoplatinum(IV) [ No CAS ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 1672 - 1676

30
[ 61825-94-3 ]
[ 7722-84-1 ]
[ 79-08-3 ]
2-bromoaceto-[(1R,2R)-cyclohexane-1,2-diamine-N,N']hydroxidooxalatoplatinum(IV) [ No CAS ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 1672 - 1676

31
[ 61825-94-3 ]
[ 86-87-3 ]
[ 7722-84-1 ]
[(1R,2R)-cyclohexane-1,2-diamine-N,N']naphthyleneacetohydroxidooxalatoplatinum(IV) [ No CAS ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 1672 - 1676

32
[ 61825-94-3 ]
[ 7722-84-1 ]
[(1R,2R)-cyclohexane-1,2-diamine-N,N']dihydroxidooxalato-platinum(IV),trans-[Pt(OH)2(ox)(R,R-chxn)] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	In water; at 50℃; for 1h;	Oxaliplatin (0.5 g, 1.25 mmol) was oxidised with 18 mL of 30 % H2O2 and 12 mL of water as previously reported [2]. The reaction mixture was stirred for 1 h at 50 C. The clear solution was then concentrated using a rotary evaporator the desired product was precipitated by adding ethanol. The white precipitate formed was filtered off, washed with ethanol and diethyl ether and dried under vacuum. Yield 0.49 g, 90 %. 1H NMR (400 MHz, DMSO-d6): delta = 10.2 (s, 2 H, OH), 7.62 (2 H, NH2), 6.85 (2 H, NH2), 1.95 (d, 2 H, DACH), 1.44 (m, 4 H, DACH), 1.04 (m, 4 H, DACH). IR (cm-1): 3427 m (nuPt-OH); 3268 m, 3211m, 3150 br, 3056 br (nu N-H); 2952 m (nuC-H); 2816 m; 1716 s, 1655 s (nuC=O); 1609 m; 1554 m; 1449 m; 1390 s; 1221 s; 1065 m; 805 s, 770 (gammaC-H). ESI-MS (negative ion mode): m/z = 430.26 [M - H]-.
	In water; at 20℃; for 20.5h;Darkness;	2.58 ml of 30% aqueous hydrogen peroxide was added to a liquid obtained by suspending l-OHP (900 mg) in 12 ml of distilled water, and the mixture was stirred for 20.5 hours at room temperature in the dark. After completion of the reaction, the reaction mixture was concentrated under reduced pressure several times while water was added to the system, and a solid was obtained. The solid thus obtained was recrystallized from distilled water, and the title compound (422 mg) was obtained. 1H-NMR (D2O): delta2.74-2.72 (2H, m), 2.17 (2H, d, J=12.8 Hz), 1.54-1.45 (4H, m), 1.18-1.12 (2H, m), purity (HPLC, analysis conditions 1): >98.0%.

Reference： [1]Inorganica Chimica Acta,2019,vol. 492,p. 262 - 267
[2]Chemistry - A European Journal,2013,vol. 19,p. 1672 - 1676
[3]Journal of Medicinal Chemistry,2019,vol. 62,p. 4543 - 4554
[4]Journal of Medicinal Chemistry,2017,vol. 60,p. 5736 - 5748
[5]European Journal of Pharmaceutical Sciences,2018,vol. 124,p. 127 - 136
[6]Patent: US2018/250332,2018,A1 .Location in patent: Paragraph 0194

34
[ 61848-66-6 ]
[ 15843-43-3 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
41%	In water;	In a typical reaction, 64 mg (0.56 mmol) of (R,R)-1,2-diaminocyclohexane (dach) was dissolved in 5 mL of methanol and added dropwise to an aqueous solution (5 mL) of 232 mg (0.56 mmol) of K2PtCl4. The reaction was stirred overnight and a yellow precipitate of Pt(dach)Cl2 was collected and washed with water, ethanol, and ether. Yield 128.8 mg (61%). Equimolar (0.17 mmol) amounts of Pt(dach)Cl2 and silver oxalate were combined in ?35 mL of water in an amber vial and stirred overnight. The sample was filtered to remove the AgCl precipitate and rotovapped with heating to ?35 C to isolate Pt(dach)(ox). Yield 27.9 mg (41%) 1H NMR (D2O): 2.33 ppm (1 H, dd), 2.04 ppm (1 H, broad d), 1.56 ppm (1 H, m), 1.30 ppm (1 H, m), 1.15 ppm (1 H, m).

Reference： [1]Inorganica Chimica Acta,2013,vol. 401,p. 64 - 69

35
[ 61825-94-3 ]
[ 65-82-7 ]
[Pt((R,R)-1,2-diaminocyclohexane)(N-acetylmethionine-S)₂] [ No CAS ]

Reference： [1]Inorganica Chimica Acta,2013,vol. 401,p. 64 - 69

36
[ 61825-94-3 ]
[ 65-82-7 ]
[Pt((R,R)-1,2-diaminocyclohexane)(N-acetylmethionine-S)₂] [ No CAS ]
[Pt((R,R)-1,2-diaminocyclohexane)(N-acetylmethionine-S,N)] [ No CAS ]

Reference： [1]Inorganica Chimica Acta,2013,vol. 401,p. 64 - 69

37
[ 61825-94-3 ]
[ 111263-58-2 ]

Reference： [1]European Journal of Inorganic Chemistry,2014,p. 484 - 492

38
[ 79-21-0 ]
[ 61825-94-3 ]
(OC-6-44)-acetato[(1R,2R)-cyclohexane-1,2-diamine]hydroxidooxalatoplatinum(IV) [ No CAS ]

Reference： [1]European Journal of Inorganic Chemistry,2014,p. 484 - 492

39
[ 61825-94-3 ]
5'-UGAACUUAGUACGAGAGGAACAGUUCACCCCCCGCCGCGAAGCUACCAUCCGCU-3' [ No CAS ]
Pt(II) bound 5'-UGAACUUAGUACGAGAGGAACAGUUCACCCCCCGCCGCGAAGCUACCAUCCGCU-3' [ No CAS ]

Reference： [1]ACS Chemical Biology,2014,vol. 9,p. 2404 - 2411

40
[ 61825-94-3 ]
Gly-Gly-Asn-Cys-Cys [ No CAS ]
oxaliplatin MAP-CDDP GGNCC [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 3: Formation of cisplatin, carboplatin, and <strong>[61825-94-3]oxaliplatin</strong> preactivated Pt-MAP complexes. [00208] Carboplatin and <strong>[61825-94-3]oxaliplatin</strong> have been bound to MAP (FIGURE 10). Transfer reactions were performed using the same reaction conditions as cisplatin. While the fully formed Pt-MAP complex has a maximum peak intensity at 305 nm, the CDDP-MAP complex has a of 288 nm (FIGURE 10). Carboplatin-MAP, which has two primary amine ligands identical to those on cisplatin, also exhibits a theta 288 nm. Oxaliplatin-MAP, with the bidentate diaminocyclohexyl ligand, has a max of 280 nm. While cisplatin has chloride ligands, which can easily be displaced by the thiols of MAP, carboplatin and <strong>[61825-94-3]oxaliplatin</strong> have bidentate oxygen ligands, which are much slower in replacement due to the stability imparted by the bidentecity of the oxygen ligands. The similarities of the absorption profiles of compounds with the same nitrogen ligands suggests that the nitrogen ligands are retained and the oxygen/halogen ligands are replaced by the thiol groups of MAP (FIGURE 16). This conclusion is supported by the slow growth of a yellow color that coincides with transfer to form a MAP-derivative. The <strong>[61825-94-3]oxaliplatin</strong> and carboplatin transfer occurred over the course of days to weeks.

Reference： [1]Patent: WO2015/81117,2015,A2 .Location in patent: Paragraph 0023; 00208

41
[ 61825-94-3 ]
[ 128-08-5 ]
trans-[Pt(trans-(1R,2R)-1,2-cyclohexanediammine)(oxalate)Br₂] [ No CAS ]

Reference： [1]Dalton Transactions,2015,vol. 44,p. 19918 - 19926

42
[ 61825-94-3 ]
[ 128-08-5 ]
[ 7732-18-5 ]
trans-[Pt(trans-(1R,2R)-1,2-cyclohexanediammine)(oxalate)(OH)Br] [ No CAS ]

Reference： [1]Dalton Transactions,2015,vol. 44,p. 19918 - 19926

43
[ 61825-94-3 ]
[ 70-18-8 ]
[ 85-32-5 ]
C₂₆H₄₆N₈O₁₂PtS₂ [ No CAS ]
C₃₂H₆₀N₁₀O₁₂Pt₂S₂⁽²⁺⁾ [ No CAS ]
[Pt((1R,2R)-diaminocyclohexane)(guanosine 5'-monophosphate)₂] [ No CAS ]
Pt⁽²⁺⁾*C₆H₁₄N₂*C₁₀H₁₆N₃O₆S^(1-) [ No CAS ]

Reference： [1]Journal of Inorganic Biochemistry,2016,vol. 157,p. 1 - 7

44
[ 61825-94-3 ]
[ 7722-84-1 ]
[ 64-19-7 ]
[(1R,2R)-cyclohexane-1,2-diamine-N,N']dihydroxidooxalato-platinum(IV),trans-[Pt(OH)2(ox)(R,R-chxn)] [ No CAS ]
(OC-6-44)-acetato[(1R,2R)-cyclohexane-1,2-diamine]hydroxidooxalatoplatinum(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; at 20℃; for 48h;Darkness;	[00227] Another example of a compound taught herein was synthesized starting with <strong>[61825-94-3]oxaliplatin</strong> (1 .0 g, 2.52 mmol, 1 equiv) that was dissolved in acetic acid (6 mL, 100 mmol, 40 equiv) and reacted with 30% H202 (1 mL, 12.6 mmol, 5 equiv). The reaction mixture was covered with aluminium foil and stirred at room temperature for 24 hours. Following this reaction, more acetic acid (3 mL, 50 mmol, 20 equiv) and 30% H202 (1 mL, 12.6 mmol, 5 equiv) were added and the reaction mixture was stirred for an additional 24 hours. The suspension was filtered and the white solid residue was washed with diethylether (Et20) to yield hydroxy(acetoxy)<strong>[61825-94-3]oxaliplatin</strong> (878 mg, 74% yield, 70% pure). 1H NMR (500 MHz, DMF-d7) delta 10.42 (brs, 2H), 8.93 (m, 1 H), 8.39 (brs, 1 H), 7.96 (brs, 1 H), 7.26 (brs, 1 H), 2.91 -2.80 (m, 2H), 2.31 -2.22 (m,2H), 1 .98 (s, 3H), 1 .89 (s, 3H), 1 .73-1 .49 (m, 4H), 1 .34-1 .21 (m, 2H); HPLC-MS 91 %, m/z for Ci0H18N2O7Pt [(M+H)+] = 474.

Reference： [1]Patent: WO2015/200250,2015,A1 .Location in patent: Paragraph 00227

45
[ 61825-94-3 ]
[ 16024-56-9 ]
[ 7722-84-1 ]
hydroxy(2-methylethoxyacetoxy)oxaliplatin(IV) [ No CAS ]
C₁₈H₃₂N₂O₁₂Pt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; for 16h;	[00242] Oxaliplatin (2.05 g, 5.00 mmol, 1 .00 equiv) was suspended in 2- <strong>[16024-56-9]methoxyethoxyacetic acid</strong> (22.7 mL, 200 mmol, 40.0 equiv), then hydrogen peroxide (30% w/w in water, 0.775 mL, 25 mmol, 5.0 equiv) was added and solution was stirred for 16 hours. MTBE (175 mL) was added and the filtrate was decanted. The gummy residue was dissolved in DMF (5 mL) and added dropwise onto EtOAc (125 mL). The resulting precipitate was filtered, rinsed with EtOAc (3 X 20 mL) and dried under vacuum to afford a white solid (1 .75 g). HPLC/MS (method B): 2.29 minutes, M+H = 547, 548, 549 and 2.81 minutes, M+H = 663, 664, 665. The solid consists of a 1 :1 mixture of desired product and bis acylation product and was used in that composition for next step.

Reference： [1]Patent: WO2015/200250,2015,A1 .Location in patent: Paragraph 00242

46
[ 61825-94-3 ]
[ 7722-84-1 ]
[ 625-45-6 ]
methoxyacetate hydroxy oxaliplatin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
400 mg	In water; for 1h;	[00225] Step 1 : Oxaliplatin (300 mg, 0.76 mmol, 1 .0 equiv) was suspended in methoxyacetic acid (3.40 g, 37.8 mmol, 50 equiv), then hydrogen peroxide (30% w/w in water, 0.13 mL, 3.8 mmol, 5.0 equiv) was added and solution was stirred for 1 hour. Diethyl ether was added and resulting precipitate was filtered and dried to afford a white solid (400 mg).

Reference： [1]Patent: WO2015/200250,2015,A1 .Location in patent: Paragraph 00225

47
[ 61825-94-3 ]
[ 128-09-6 ]
[ 107-21-1 ]
cis,trans,cis-[Pt(ethanedioato)Cl(2-hydroxyethanolato)(1R,2R-diaminocyclohexane)] [ No CAS ]

Reference： [1]International Journal of Molecular Sciences,2016,vol. 17

48
[ 61825-94-3 ]
[ 7722-84-1 ]
(SP-4-2)-(trans-R,R-cyclohexane-1,2-diamine)dihydroxo(oxalato) platinum(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	In water; at 60℃; for 4h;	To a 250 mL round-bottom flask, 1.0 g of <strong>[61825-94-3]oxaliplatin</strong> 6-2, 30 mL of distilled water was added, and stirred to disperse, and 50 mL of 30% hydrogen peroxide was slowly added dropwise to the reaction system, and the temperature was raised to 60 C. and the reaction was stirred for 4 h. The reaction was stopped and crystallized at 4 C for 12 hours. A yellow solid was obtained by filtration and separation. Add appropriate amount of distilled water and heat to 80 C to dissolve it. After crystallizing at 4 C for 12 hours, white crystals of compound 5-2 (0.77g, 71%).
	at 20℃; for 8h;	Oxaliplatin(764mg, 2mmol) placed in a flask, and then 30% hydrogen peroxide was added 10mL, After stirring at room temperature for 8 h, filtered to remove the hydrogen peroxide to give Oxaliplatin (IV) - (OH)2 Yellow powder.
	at 20℃; for 24h;	Oxaliplatin (1.0 g, 2.52 mmol, 1 equiv.) that was dissolved in acetic acid (6 mL, 100 mmol) and reacted with 30% H2O2 (1 mL, 12.6 mmol). The reaction mixture was covered with aluminium foil and stirred at room temperature for 24 hours. Following this reaction, more acetic acid (3 mL, 50 mmol) and 30% H2O2 (1 mL, 12.6 mmol) were added and the reaction mixture was stirred for an additional 24 hours. The suspension was filtered and the white solid residue was washed with diethyl ether to yield 31? (878 mg, 74% yield, 70% pure).1H NMR (500 MHz, DMF-d7) delta 10.42 (brs, 2H), 8.93 (m, 1H), 8.39 (brs, 1H), 7.96 (brs, 1H), 7.26 (brs, 1H), 2.91-2.80 (m, 2H), 2.31-2.22 (m,2H), 1.98 (s, 3H), 1.89 (s, 3H), 1.73-1.49 (m, 4H), 1.34-1.21 (m, 2H); HPLC-MS 91%, LCMS M/Z = 474.2 [M + 1].

Reference： [1]Journal of the American Chemical Society,2020,vol. 142,p. 7803 - 7812
[2]Angewandte Chemie - International Edition,2018,vol. 57,p. 9098 - 9102
Angew. Chem.,2018,vol. 130,p. 9236 - 9240,5
[3]Patent: CN111072725,2020,A .Location in patent: Paragraph 0090; 0097-0099
[4]Patent: CN105753922,2016,A .Location in patent: Paragraph 0086; 0087
[5]Patent: CN103588818,2016,B .Location in patent: Paragraph 0121; 0122
[6]Patent: WO2017/180834,2017,A1 .Location in patent: Paragraph 00365
[7]Chemical Communications,2018,vol. 54,p. 9242 - 9245
[8]Inorganic Chemistry,2019,vol. 58,p. 7886 - 7894
[9]Bioorganic Chemistry,2020,vol. 99

49
[ 61825-94-3 ]
human copper chaperone atox1 [ No CAS ]
dimeric Pt2+ ion bound human copper chaperone atox1 [ No CAS ]
Pt2+ ion bound human copper chaperone atox1 [ No CAS ]

Reference： [1]Inorganic Chemistry,2016,vol. 55,p. 6563 - 6573

50
[ 61825-94-3 ]
[ 33430-61-4 ]
C₂₆H₃₈N₁₂O₁₄P₂Pt^(2-) [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 125,p. 372 - 384

51
[ 61825-94-3 ]
[ 128-09-6 ]
[ 7732-18-5 ]
trans,cis,cis-[PtCl(OH)(R,R-dach)(ox)] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
114 mg	at 20℃; for 4h;Darkness;	N-chlorosuccinimide (66.8 mg) was dissolved in 14 ml of distilled water, a liquid obtained by suspending l-OHP (200 mg) in 6 ml of distilled water was added to the solution, and the mixture was stirred for 4 hours at room temperature in the dark. After completion of the reaction, insoluble matters in the reaction liquid were separated by filtration, the filtrate was concentrated under reduced pressure, and thereby a solid was obtained. The solid thus obtained was recrystallized from ethanol/water, and thus the title compound (114 mg) was obtained. 1H-NMR (D2O): delta2.89-2.72 (2H, m), 2.15 (2H, d, J=12.2 Hz), 1.53-1.41 (4H, m), 0.97-0.90 (2H, m), MS(ESI):450 (M+1), 451 (M+2), purity (HPLC, analysis conditions 2): 99.4%.

Reference： [1]Bioconjugate Chemistry,2016,vol. 27,p. 2132 - 2148
[2]Patent: US2018/250332,2018,A1 .Location in patent: Paragraph 0160

52
[ 61825-94-3 ]
[ 7732-18-5 ]
[ 7722-84-1 ]
[ 625-45-6 ]
methoxy acetate hydroxy oxaliplatin [ No CAS ]

Reference： [1]Patent: WO2016/209935,2016,A1 .Location in patent: Paragraph 00299

53
[ 61825-94-3 ]
[ 7732-18-5 ]
[ 7722-84-1 ]
[ 64-19-7 ]
acetate[(1R,2R)-cyclohexane-1,2-diamine-N,N]-hydroxidooxalatoplatinum (IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 20℃; for 24h;	Another example of a compound taught herein was synthesized starting with <strong>[61825-94-3]oxaliplatin</strong> (1.0 g, 2.52 mmol, 1 equiv.) that was dissolved in acetic acid (6 mL, 100 mmol, 40 equiv.) and reacted with 30% H2O2 (1 mL, 12.6 mmol, 5 equiv.). The reaction mixture was covered with aluminium foil and stirred at room temperature for 24 hours. Following this reaction, more acetic acid (3 mL, 50 mmol, 20 equiv.) and 30% H2O2 (1 mL, 12.6 mmol, 5 equiv.) were added and the reaction mixture was stirred for an additional 24 hours. The suspension was filtered and the white solid residue was washed with diethylether (Et20) to yield hydroxy(acetoxy)<strong>[61825-94-3]oxaliplatin</strong> (878 mg, 74% yield, 70% pure). NMR (500 MHz, DMF-d7) delta 10.42 (brs, 2H), 8.93 (m, 1H), 8.39 (brs, 1H), 7.96 (brs, 1H), 7.26 (brs, 1H), 2.91-2.80 (m, 2H), 2.31-2.22 (m,2H), 1.98 (s, 3H), 1.89 (s, 3H), 1.73-1.49 (m, 4H), 1.34-1.21 (m, 2H); HPLC-MS 91%, m/z for CioHis^OvPt [(M+H)+] = 474.2.

Reference： [1]Patent: WO2016/209935,2016,A1 .Location in patent: Paragraph 00301

54
[ 61825-94-3 ]
[ 16024-56-9 ]
C₁₅H₁₉NO₈ [ No CAS ]
[ 7732-18-5 ]
[ 7722-84-1 ]
C₂₃H₃₃N₃O₁₄Pt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
131 mg		2-Hydroxyethyl maleimide (120 mg, 0.85 mmol, 2.00 equiv.) was suspended in THF (4.0 mL) then N-methyl morpholine (93 uL, 0.85 mmol, 2.0 equiv.) was added followed by succinic anhydride (85 mg, 0.85 mmol, 2.0 equiv.). The solution was stirred at room temperature for 16 hours, then N-methyl morpholine (93 uL, 0.85 mmol, 2.0 equiv.) was added followed by isobutyl chloroformate (110 uL, 0.85 mmol, 2.0 equiv.) and the solution was stirred at room temperature for 45 minutes. Water (10 mL) and ethyl acetate (10 mL) were added and the layers were separated. Solvent was then evaporated, then the activated ester was dissolved in DMF and hydroxy(2- methylethoxyacetoxy)oxalplatin(IV) (233 mg, 0.43 mmol, 1.0 equiv.) was added and solution was stirred sat 50 C for 18 hours. Solvent was evaporated from this mixture and the crude product was purified on silica gel (0-8% MeOH/DCM gradient) to afford the desired product with residual MeOH. The residue was dissolved in MeOH (2 mL) and the resulting solution was added to TBME (50 mL) to obtain a white precipitate (compound 13) that was filtered and dried under vacuum. Compound 13 was obtained as an off- white solid (131 mg, 40% yield). HPLC/MS (method B): 3.41 minutes, M+H = 771

Reference： [1]Patent: WO2016/209935,2016,A1 .Location in patent: Paragraph 00317

55
[ 61825-94-3 ]
[ 16024-56-9 ]
[ 7732-18-5 ]
[ 7722-84-1 ]
bis(2-methylethoxyacetoxy)oxalplatin(IV) [ No CAS ]
hydroxy(2-methylethoxyacetoxy)oxalplatin(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	for 16h;	Oxaliplatin (2.05 g, 5.00 mmol, 1.00 equiv.) was suspended in 2- <strong>[16024-56-9]methoxyethoxyacetic acid</strong> (22.7 mL, 200 mmol, 40.0 equiv.), then hydrogen peroxide (30% w/w in water, 0.775 mL, 25 mmol, 5.0 equiv.) was added and solution was stirred for 16 hours. MTBE (175 mL) was added and the filtrate was decanted. The gummy residue was dissolved in DMF (5 mL) and added dropwise onto EtOAc (125 mL). The resulting precipitate was filtered, rinsed with EtOAc (3 X 20 mL) and dried under vacuum to afford a white solid (1.75 g). HPLC/MS (method B): 2.29 minutes, M+H = 547, 548, 549 and 2.81 minutes, M+H = 663, 664, 665. The solid consists of a 1 : 1 mixture of desired product and bis acylation product and was used in that composition for next step.

Reference： [1]Patent: WO2016/209935,2016,A1 .Location in patent: Paragraph 00316

56
[ 108-30-5 ]
[ 61825-94-3 ]
C₁₆H₂₄N₂O₁₂Pt [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 12626 - 12631
Angew. Chem.,2016,vol. 128,p. 12816 - 12821,6

57
[ 108-30-5 ]
[ 61825-94-3 ]
C₁₄H₂₂N₂O₁₀Pt [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 12626 - 12631
Angew. Chem.,2016,vol. 128,p. 12816 - 12821,6

58
[ 108-30-5 ]
[ 61825-94-3 ]
C₁₂H₂₀N₂O₈Pt [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 12626 - 12631
Angew. Chem.,2016,vol. 128,p. 12816 - 12821,6

59
[ 61825-94-3 ]
[ 123-62-6 ]
C₁₅H₂₆N₂O₈Pt [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 12626 - 12631
Angew. Chem.,2016,vol. 128,p. 12816 - 12821,6

60
[ 61825-94-3 ]
5'-TCCGGCCT-3' [ No CAS ]
5'-TCCG((diamino-1,2-cyclohexane)-Pt)GCCT-3' [ No CAS ]
5'-TCCG((diamino-1,2-cyclohexane)-Pt)G((diamino-1,2-cyclohexane)-Pt)CCT-3' [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 3033 - 3044

61
[ 61825-94-3 ]
5'-UCAGGUACUCAGUCAUCCACAdTdT-3' [ No CAS ]
[ 7732-18-5 ]
[ 2864-70-2 ]
C₃₉H₄₉N₁₇O₂₉P₄*2C₆H₁₄N₂*2Pt*2H₂O [ No CAS ]
C₃₉H₄₉N₁₇O₂₉P₄*C₆H₁₄N₂*Pt [ No CAS ]
C₂₉H₃₇N₁₂O₂₂P₃*C₆H₁₄N₂*Pt [ No CAS ]
5'-AU-3' [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 3033 - 3044

63
[ 61825-94-3 ]
[ 5550-12-9 ]
(diamino-1,2-cyclohexane)-platinum(II)(5'-guanosine monophosphate )2 [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 3033 - 3044

64
[ 108-30-5 ]
[ 61825-94-3 ]
[ 7722-84-1 ]
OxaPt(IV) [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 3033 - 3044

65
[ 61825-94-3 ]
[ 128-09-6 ]
trans-Pt(IV)Cl₂(oxalato)(l-1,2-cyclohexanediamine) [ No CAS ]

Reference： [1]European Journal of Inorganic Chemistry,2017,vol. 2017,p. 1706 - 1712

66
[ 61825-94-3 ]
[ 516-12-1 ]
trans-[Pt(trans-(1R, 2R)-1,2-cyclohexanediammine)(oxalate)(C₄H₄NO₂)l] [ No CAS ]

Reference： [1]European Journal of Inorganic Chemistry,2017,vol. 2017,p. 1706 - 1712

67
[ 61825-94-3 ]
[ 128-09-6 ]
[ 7732-18-5 ]
hydroxychlorooxaliplatin(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89.3%	at 20℃; for 3h;Darkness;	N-chlorosuccinimide (29.38mg, 0.22mmol) dissolved in 14mL of water was added to a suspension of <strong>[61825-94-3]oxaliplatin</strong> (84.40mg, 0.22mmol) in 6mL of water. The reaction was stirred at room temperature for 3h in the dark. The solid residue was removed by centrifugation and the solution was evaporated to dryness to get a pale yellow solid that was washed with ethanol and diethylether. Yield: 89.3%. 1H NMR (300MHz, DMSO-d6): delta 8.01-7.57 (m, 2H), 7.31-6.83 (m, 2H), 2.62-2.54 (m, 2H), 1.99 (d, J=15.0Hz, 2H), 1.64-1.34 (m, 4H), 1.11-0.99 (m, 2H).
89.2%	at 20℃;Inert atmosphere;	Oxaliplatin (1.0 g, 2.5 mmol) was suspended in distilled water 150 mL and stirred at room temperature. N-chloro succinimide (NCS) solution(0.392 g, 2.94 mmol) in distilled water 150 mL was added to reaction system dropwise and theresultant mixture was stirred overnight at room temperature. After that, thesolid was filtrated and the solution was concentrated under vacuum. The residuewas washed with ethanol and ethylether. The product O1 was obtained as a yellow solid (1.07 g, 89.2%).
89%	at 60℃;Darkness;	Put 1.15 g (2.67 mmol) of <strong>[61825-94-3]oxaliplatin</strong> in a reaction flask, add 172.5 mL of distilled water and stir well. 0.392 g (2.94 mmol) of N-chlorosuccinimide (NCS) was dissolved in 150 mL of distilled water, and it was slowly added to the <strong>[61825-94-3]oxaliplatin</strong> solution. The system was stirred overnight in the dark, and the solids were filtered off and the solution was reduced. Spin dry to obtain a yellow solid. The solid was washed with ethanol and diethyl ether and dried to give the final pale yellow product 4c-1 (1.07 g, 89%).

82%

Darkness;

Place 1.15g (2.67mmol) of [61825-94-3]oxaliplatin 6-2 in the reaction bottle, add 172.5mL of distilled water and stir to mix. Dissolve 0.392g (2.94mmol) of N-chlorosuccinimide (NCS) in 150mL of distilled water and slowly add it to the [61825-94-3]oxaliplatin solution. The system was stirred overnight in the dark, the solid was filtered off, the solution was reduced Spin dry to give a yellow solid. The solid was washed with ethanol and ether separately, and dried to obtain the final light yellow product 3a-2 (0.98 g, 82%).

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 137,p. 167 - 175
[2]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29
[3]Patent: CN110041375,2019,A .Location in patent: Paragraph 0065; 0072-0074
[4]Patent: CN111072725,2020,A .Location in patent: Paragraph 0071; 00780080
[5]Dalton Transactions,2020,vol. 49,p. 5192 - 5204
[6]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 2507 - 2517

68
[ 67-56-1 ]
[ 61825-94-3 ]
oxalato[(1R,2R)-1,2-cyclohexanediamine-KN,KN']hydroxy,methoxyplatinum [ No CAS ]

Reference： [1]Patent: WO2017/97986,2017,A1 .Location in patent: Page/Page column 64

69
[ 61825-94-3 ]
[ 64-19-7 ]
(OC-6-44)-acetato[(1R,2R)-cyclohexane-1,2-diamine]hydroxidooxalatoplatinum(IV) [ No CAS ]

Reference： [1]Patent: WO2017/97986,2017,A1 .Location in patent: Page/Page column 66

70
[ 61825-94-3 ]
vitamin B₁₂ [ No CAS ]
C₆₉H₁₀₁CoN₁₆O₁₄PPt⁽¹⁺⁾ [ No CAS ]
C₆₉H₁₀₂CoN₁₆O₁₄PPt⁽¹⁺⁾ [ No CAS ]

Reference： [1]RSC Advances,2017,vol. 7,p. 53658 - 53666

71
[ 61825-94-3 ]
[ 259886-50-5 ]
CB[7]-L-OHP [ No CAS ]

Reference： [1]Australian Journal of Chemistry,2017,vol. 70,p. 677 - 682

72
bis(3-carboxypropanoato)(trans-1R,2R-diaminocyclohexane)oxalatoplatinum(IV) [ No CAS ]
[ 61825-94-3 ]

Reference： [1]Chemical Communications,2018,vol. 54,p. 9242 - 9245

73
[ 61825-94-3 ]
[ 7722-84-1 ]
[ 111263-58-2 ]

Reference： [1]Chemical Communications,2018,vol. 54,p. 5369 - 5372

74
[ 61825-94-3 ]
[ 7720-24-3 ]
C₂₆H₃₈N₁₂O₁₄P₂Pt [ No CAS ]
C₁₆H₂₆N₇O₇PPt [ No CAS ]

Reference： [1]Chemical Communications,2018,vol. 54,p. 12762 - 12765

75
C₇₆H₁₂₄N₆O₁₄Pt [ No CAS ]
[ 61825-94-3 ]
[ 1239481-01-6 ]

Reference： [1]Chemical Communications,2018,vol. 54,p. 12762 - 12765

76
[ 61825-94-3 ]
[ 7732-18-5 ]
[ 7722-84-1 ]
[(1R,2R)-cyclohexane-1,2-diamine-N,N']dihydroxidooxalato-platinum(IV),trans-[Pt(OH)2(ox)(R,R-chxn)] [ No CAS ]

Reference： [1]Applied Organometallic Chemistry,2019,vol. 33

77
[Pt((1R,2R)-(-)-1,2-diaminocyclohexane)(H₂O)₂]SO₄ [ No CAS ]
[ 144-62-7 ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
33%	With sodium hydroxide; at 20℃; for 20h;pH 6;	Oxaliplatin was synthesized as described in patent PCT/EP2010/003753 [4] with slight modifications. K2PtCl4 (2 g, 4.8 mmol) was dissolved in 40 mL of water. To this solution diaminocyclohexane (DACH) (5.4 g, 4.8 mmol) in 20 mL ethanol was added and the mixture was allowed to react for 6 h at rt. During the reaction, the product (DACH)PtCl2 precipitated. Then (DACH)PtCl2 was suspended in 60 mL of water, 1.43 g Ag2SO4 was added and the solution was stirred at room temperature for 20 h under light exclusion. This led to the formation of soluble [Pt(DACH)(H2O)2]SO4 complex accompanied by the formation of poorly soluble AgCl, which was filtered off. To the filtrate 0.46 g (3.7 mmol) of oxalic acid dihydrate and 0.5 M NaOH were added until the pH reached 6. The mixture was stirred at r.t. for further 20 h. The solution was concentrated using a rotary evaporator, until the final product [Pt(DACH)(ox)] precipitated. This was filtered off, washed with water and acetone and dried under vacuum. Yield: 0.63 g (33 %). Purity was confirmed by IR-spectroscopy and elemental analysis. IR (cm-1): 3211m, 3160 m, 3081 s (nuN-H); 2960 w (nuC-H); 2929 m; 2864 m; 1696 s, 1660 s, 1653 m (nuC=O); 1609 m; 1373 s; 1226 s; 1069 s; 808 s, 742 (gammaC-H). Anal. Calcd. for C8H14N2O4Pt: C 24.19, H 3.55, N 7.05 %. Found C 23.95, H 3.65, N 7.01 %.

Reference： [1]Applied Organometallic Chemistry,2019,vol. 33
[2]Inorganica Chimica Acta,2019,vol. 492,p. 262 - 267

78
[ 61825-94-3 ]
(SP-4-2)-(trans-R,R-cyclohexane-1,2-diamine)dihydroxo(oxalato) platinum(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dihydrogen peroxide; In water; at 30℃; for 12h;Darkness;	Weigh <strong>[61825-94-3]oxaliplatin</strong> 500mg,Suspended in 10ml of deionized water,Add 3 ml of 30% hydrogen peroxide, place in a 50 ml round bottom flask, stir the reaction at 30 C for 12 hours in the dark, remove the solvent by rotary evaporation, and add the methanol to dissolve the obtained substance.Precipitate with diethyl ether,Oxaliplatin is oxidized by vacuum drying.

Reference： [1]Patent: CN106074379,2019,B .Location in patent: Paragraph 0030; 0055; 0056

79
[ 61825-94-3 ]
[ 7722-84-1 ]
[Pt(1,2-diaminocyclohexane)(OH)2(ox)] [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 5176 - 5190

80
[ 61825-94-3 ]
[ 7732-18-5 ]
[ 7722-84-1 ]
(SP-4-2)-(trans-R,R-cyclohexane-1,2-diamine)dihydroxo(oxalato) platinum(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	at 60℃; for 4h;	To a 250 mL round-bottomed flask was added 1.0 g of <strong>[61825-94-3]oxaliplatin</strong> and 30 mL of distilled water, which were stirred to disperse, and 50 mL of a hydrogen peroxide solution having a concentration of 30% was slowly added dropwise to the reaction system. The temperature was raised to 60 C. and the reaction was stirred for 4 h. Stop the reaction, crystallize at -4 C for 12 hours, filter to obtain a yellow solid, add an appropriate amount of distilled water, heat to 80 C to dissolve, crystallize at 4 C for 12 hours, and filter to obtain compound 4a-2 white crystals (0.85g , 78%).

Reference： [1]Patent: CN110041375,2019,A .Location in patent: Paragraph 0065; 0069-0071
[2]Dalton Transactions,2020,vol. 49,p. 5192 - 5204
[3]Angewandte Chemie - International Edition,2019,vol. 58,p. 14189 - 14192
Angew. Chem.,2019,vol. 131,p. 14327 - 14330,4

81
[ 61825-94-3 ]
[ 7722-84-1 ]
[ 64-19-7 ]
acetate[(1R,2R)-cyclohexane-1,2-diamine-N,N]-hydroxidooxalatoplatinum (IV) [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 14189 - 14192
Angew. Chem.,2019,vol. 131,p. 14327 - 14330,4

82
C₁₅H₂₆N₂O₈Pt [ No CAS ]
[ 61825-94-3 ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 14189 - 14192
Angew. Chem.,2019,vol. 131,p. 14327 - 14330,4

83
phorbiplatin [ No CAS ]
[ 61825-94-3 ]

Reference： [1]Chem,2019,vol. 5,p. 3151 - 3165

84
[ 61825-94-3 ]
[ 64-17-5 ]
[ 7722-84-1 ]
c,c,t-(1R,2R-diaminocyclohexane)oxalatoethoxidohydroxoplatinum(IV) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	In water; at 70℃; for 5h;	A 50% wt/v H2O2 (1 mL) solution was added dropwise to a suspensionof <strong>[61825-94-3]oxaliplatin</strong> (0.38 g, 0.96 mmol) in EtOH (400 mL). The reactionwas stirred for 5 h at 70 C. The resultant clear pale yellow solutionwas concentrated to near dryness in vacuo giving an oily residue.The subsequent addition of Et2O (20 mL) precipitated a light yellowsolid which was collected by vacuum filtration, and washed with coldEtOH and Et2O (0.405 g, 92%).1H NMR (400 MHz, DMSO-d6) delta: 10.24 (s, 1H, OH), 7.84 (br s, 1H,NH), 7.38 (br s, 1H, NH), 6.99 (br s, 1H, NH), 6.44 (br s, 1H, NH), 3.19(q, 3J = 8 Hz, 2H, OEt CH2), 1.94 (dd, 3J = 20 Hz, 4J = 8 Hz, 2H,DACH CH), 1.39 (m, 5H, DACH CH & OEt CH3), 1.04 (m, 6H, DACHCH) ppm. 195Pt NMR (86 MHz, DMSO-d6) delta: 1296.79 ppm. EA calc. %for C10H20N2O6Pt·2H2O requires C, 24.25; H, 4.88; N, 5.65, found C,24.07; H, 4.49; N, 5.51%.

Reference： [1]Inorganica Chimica Acta,2020,vol. 505

85
C₄₃H₅₀N₆O₉Pt [ No CAS ]
[ 61825-94-3 ]
pyropheophorbide a acid [ No CAS ]

Reference： [1]Chem,2019,vol. 5,p. 3151 - 3165

86
[ 61825-94-3 ]
[ 404950-80-7 ]
[Pt^II((1R,2R)-(–)-1,2-diaminocyclohexane)((E)-N-hydroxy-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide_-2H)] [ No CAS ]

Reference： [1]Dalton Transactions,2020,vol. 49,p. 5703 - 5710

87
[ CAS Unavailable ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium L-ascorbate In aq. phosphate buffer at 37℃; Darkness;

Reference： [1]Chen, Shu; Gunawan, Yuliana F.; Tse, Man-Kit; Yao, Houzong; Zhou, Qiyuan; Zhu, Guangyu [Inorganic Chemistry, 2020]

88
[ CAS Unavailable ]
[ 61825-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium L-ascorbate In aq. phosphate buffer at 37℃; Darkness;

Reference： [1]Chen, Shu; Gunawan, Yuliana F.; Tse, Man-Kit; Yao, Houzong; Zhou, Qiyuan; Zhu, Guangyu [Inorganic Chemistry, 2020]

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H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 61825-94-3 ] {[proInfo.proName]}

Quality Control of [ 61825-94-3 ]

Related Doc. of [ 61825-94-3 ]

Product Details of [ 61825-94-3 ]

Calculated chemistry of [ 61825-94-3 ]

Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 61825-94-3 ]

Application In Synthesis of [ 61825-94-3 ]

[ 61825-94-3 ] Synthesis Path-Upstream 1~19

[ 61825-94-3 ] Synthesis Path-Downstream 1~88

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