New method for preparing picoplatin

Abstract

The invention relates to a novel method for preparing picoplatin. The technical scheme adopts following steps of: firstly generating potassium tetraiodoplatinate by reacting potassium tetrachloro platinum with potassium iodide to improve the activity of reactants; generating triiodo (2-picoline) platinum (II) potassium by reacting the potassium tetraiodoplatinate with 2- picoline; generating Cis-2 iodine-ammonia and (2-picoline) platinum (II) by reacting triiodo (2-picoline) platinum (II) potassium with ammonia water; adding the Cis-2 iodine-ammonia and the (2-picoline) platinum (II) togetherto deionized water; stirring the deionized water for reaction at the room temperature; filtering silver iodide precipitate when the reaction is completed; and adding potassium chloride so as to gradually separate out crystallized products of the picoplatin. In the invention, the reaction is more complete, the utilization of the platinum and the yield are enhanced, the products do not have silver irons, and the problem that the silver irons are exceeded needs not to be worried.

Description

technical field

[0001] The invention relates to a preparation method of antitumor drug picoplatin, belonging to the technical field of pharmaceutical engineering. Background technique

[0002] Picoplatin is a new generation of platinum anticancer drugs developed after cisplatin, carboplatin and oxaliplatin. Picoplatin is also known as: picoplatin, JM473, AMD473, ZD0473, etc., the English name is Picoplatin, the chemical name is cis-dichloro-ammonia, (2-picoline) platinum (II), molecular weight: 376.16, CAS : 181630-15-9, its chemical structure is as follows:

[0003]

[0004] Picoplatin was first researched and developed by Canadian AmorMed company. It is designed to reduce drug resistance through steric hindrance effect. Compared with cisplatin, picoplatin 2-picoline replaces one ammonia of cisplatin, and the methyl group is located on Pt. - Above the N plane, the steric hindrance of the reaction between the drug and other substances is increased, and the speed of its...

Examples

Embodiment 1

[0051] This example illustrates the preparation of picoplatin.

[0052] In the reaction flask, add K under dark conditions 2 PtCl 4 (103.8g, 0.25mol), 1500mL of deionized water, and 500mL of an aqueous solution in which KI (166g, 1mol) was dissolved was added, and the mixture was stirred at 25°C for 2 hours. 2-Methylpyridine (23.3 g, 0.25 mol) was slowly added dropwise, and the mixture was stirred at 25°C for 8 hours. Filtrate and dry under reduced pressure to obtain potassium triiodo(2-picoline)platinate(II) potassium (170.0 g, 0.24 mol) in the form of brown crystalline powder, with a yield of 96%, and keep it sealed and protected from light for future use;

[0053] Potassium triiodo (2-picoline) platinum (II) (170.0 g, 0.24 mol), 25% ammonia (16.3 g, 0.24 mol), and 2000 mL of deionized water were stirred at room temperature and protected from light. Mix evenly, stir at 25°C for 8 hours, filter, wash the filter cake with pure water, and dry under vacuum at 45°C to obtain c...

Embodiment 2

[0056] The preparation method of the picoplatin of this embodiment is the same as that of Example 1, but the reaction conditions are changed.

[0057] In the reaction flask, add K under dark conditions 2 PtCl 4 (103.8g, 0.25mol), 1500mL of deionized water, and 500mL of an aqueous solution in which KI (166g, 1mol) was dissolved was added, and the mixture was stirred at 30°C for 2 hours. 2-Methylpyridine (23.3 g, 0.25 mol) was slowly added dropwise, and the mixture was stirred at 30° C. for 8 hours. Filtrate and dry under reduced pressure to obtain potassium triiodo(2-picoline)platinate(II) potassium (163.0 g, 0.23 mol) in the form of brown crystalline powder, with a yield of 92%, and store it in an airtight and dark place for future use;

[0058] Potassium triiodo (2-picoline) platinum (II) (163.0 g, 0.23 mol), 25% ammonia (15.6 g, 0.23 mol), and 2000 mL of deionized water were stirred at room temperature and protected from light. Mix well, stir at 30°C for 8 hours, filter, ...

Embodiment 3

[0061] The preparation method of the picoplatin of this embodiment is the same as that of Example 1, but the reaction conditions are changed.

[0062] In the reaction flask, add K under dark conditions 2 PtCl 4 (103.8g, 0.25mol), 1500mL of deionized water, and 500mL of an aqueous solution in which KI (166g, 1mol) was dissolved was added, and the mixture was stirred at 15°C for 1 hour. 2-Methylpyridine (23.3 g, 0.25 mol) was slowly added dropwise, and the mixture was stirred at 15° C. for 8 hours. Filter and dry under reduced pressure to obtain potassium triiodo(2-picoline)platinate(II) potassium (172.0 g, 0.24 mol) in the form of brown crystalline powder, with a yield of 97%, and store it in a sealed and dark place for future use;

[0063] Potassium triiodo (2-picoline) platinum (II) (172.0 g, 0.24 mol), 25% ammonia (16.3 g, 0.24 mol), and 2000 mL of deionized water were stirred at room temperature and protected from light. Mix evenly, stir at 15°C for 8 hours, filter, wash...

technical field

[0001] The invention relates to a preparation method of antitumor drug picoplatin, belonging to the technical field of pharmaceutical engineering. Background technique

[0002] Picoplatin is a new generation of platinum anticancer drugs developed after cisplatin, carboplatin and oxaliplatin. Picoplatin is also known as: picoplatin, JM473, AMD473, ZD0473, etc., the English name is Picoplatin, the chemical name is cis-dichloro-ammonia, (2-picoline) platinum (II), molecular weight: 376.16, CAS : 181630-15-9, its chemical structure is as follows:

[0003]

[0004] Picoplatin was first researched and developed by Canadian AmorMed company. It is designed to reduce drug resistance through steric hindrance effect. Compared with cisplatin, picoplatin 2-picoline replaces one ammonia of cisplatin, and the methyl group is located on Pt. - Above the N plane, the steric hindrance of the reaction between the drug and other substances is increased, and the speed of its...

Examples

Embodiment 1

[0051] This example illustrates the preparation of picoplatin.

[0052] In the reaction flask, add K under dark conditions 2 PtCl 4 (103.8g, 0.25mol), 1500mL of deionized water, and 500mL of an aqueous solution in which KI (166g, 1mol) was dissolved was added, and the mixture was stirred at 25°C for 2 hours. 2-Methylpyridine (23.3 g, 0.25 mol) was slowly added dropwise, and the mixture was stirred at 25°C for 8 hours. Filtrate and dry under reduced pressure to obtain potassium triiodo(2-picoline)platinate(II) potassium (170.0 g, 0.24 mol) in the form of brown crystalline powder, with a yield of 96%, and keep it sealed and protected from light for future use;

[0053] Potassium triiodo (2-picoline) platinum (II) (170.0 g, 0.24 mol), 25% ammonia (16.3 g, 0.24 mol), and 2000 mL of deionized water were stirred at room temperature and protected from light. Mix evenly, stir at 25°C for 8 hours, filter, wash the filter cake with pure water, and dry under vacuum at 45°C to obtain c...

Embodiment 2

[0056] The preparation method of the picoplatin of this embodiment is the same as that of Example 1, but the reaction conditions are changed.

[0057] In the reaction flask, add K under dark conditions 2 PtCl 4 (103.8g, 0.25mol), 1500mL of deionized water, and 500mL of an aqueous solution in which KI (166g, 1mol) was dissolved was added, and the mixture was stirred at 30°C for 2 hours. 2-Methylpyridine (23.3 g, 0.25 mol) was slowly added dropwise, and the mixture was stirred at 30° C. for 8 hours. Filtrate and dry under reduced pressure to obtain potassium triiodo(2-picoline)platinate(II) potassium (163.0 g, 0.23 mol) in the form of brown crystalline powder, with a yield of 92%, and store it in an airtight and dark place for future use;

[0058] Potassium triiodo (2-picoline) platinum (II) (163.0 g, 0.23 mol), 25% ammonia (15.6 g, 0.23 mol), and 2000 mL of deionized water were stirred at room temperature and protected from light. Mix well, stir at 30°C for 8 hours, filter, ...

Embodiment 3

[0061] The preparation method of the picoplatin of this embodiment is the same as that of Example 1, but the reaction conditions are changed.

[0062] In the reaction flask, add K under dark conditions 2 PtCl 4 (103.8g, 0.25mol), 1500mL of deionized water, and 500mL of an aqueous solution in which KI (166g, 1mol) was dissolved was added, and the mixture was stirred at 15°C for 1 hour. 2-Methylpyridine (23.3 g, 0.25 mol) was slowly added dropwise, and the mixture was stirred at 15° C. for 8 hours. Filter and dry under reduced pressure to obtain potassium triiodo(2-picoline)platinate(II) potassium (172.0 g, 0.24 mol) in the form of brown crystalline powder, with a yield of 97%, and store it in a sealed and dark place for future use;

[0063] Potassium triiodo (2-picoline) platinum (II) (172.0 g, 0.24 mol), 25% ammonia (16.3 g, 0.24 mol), and 2000 mL of deionized water were stirred at room temperature and protected from light. Mix evenly, stir at 15°C for 8 hours, filter, wash...

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