Synthesis method of p-iodotoluene serving as methotrexate drug intermediate

A technology for p-iodotoluene and methotrexate, which is applied in the field of synthesis of p-iodotoluene, a drug intermediate of methotrexate, can solve problems such as weak G1 cell effect, reduce reaction temperature and reaction time, and improve reaction yield. efficiency, reducing the effect of intermediate links

Inactive Publication Date: 2016-04-20
CHENGDU ZHONGHENG HUATIE TECH CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, this product also has an inhibitory effect on thymonucleotide synthetase, but its inhibitory effect on RNA and protein synthesis is relatively weak. This product mainl

Method used

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  • Synthesis method of p-iodotoluene serving as methotrexate drug intermediate

Examples

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Example Embodiment

[0010] Example 1:

[0011] In a 3L reaction vessel equipped with a stirrer, a thermometer, and a dropping funnel, add 500ml of a 60% phosphoric acid solution and 1.2mol of p-toluidine (2). After dissolving, reduce the temperature of the solution to 3°C and add potassium sulfite 1.1mol of potassium sulfite solution prepared by dissolving in 300ml of water, control the reaction temperature to 15℃, continue to react for 10min after adding, slowly add 1.1mol of sodium iodate dissolved in 230ml of sodium iodate solution, control the temperature of the solution At 30°C, the stirring speed is controlled at 100rpm until the bubble generation speed in the reaction solution is slow, then adjust the solution temperature to 80°C, keep the temperature until no bubbles are generated, reduce the solution temperature to 25°C, pour the upper layer of liquid, and the remaining Add 0.2mol of potassium nitrite to the oil to make the water layer colorless, add 300ml of sodium carbonate solution with ...

Example Embodiment

[0012] Example 2:

[0013] In a 3L reaction vessel equipped with a stirrer, a thermometer, and a dropping funnel, add 500ml of 65% phosphoric acid solution and 1.2mol of p-toluidine (2). After dissolving, reduce the temperature of the solution to 5°C and add potassium sulfite 1.15mol of potassium sulfite solution prepared by dissolving in 300ml of water, control the reaction temperature to 17℃, continue to react for 12min after adding, slowly add 1.13mol of sodium iodate dissolved in 230ml of sodium iodate solution, control the temperature of the solution At 32°C, the stirring speed is controlled at 120rpm until the bubble generation speed in the reaction solution is slow, then adjust the solution temperature to 80°C, keep the temperature until no bubbles are generated, reduce the solution temperature to 26°C, pour the upper layer of liquid, and the remaining Add 0.25 mol of potassium nitrite to the oil to make the water layer colorless, add 300ml of 40% sodium carbonate solution...

Example Embodiment

[0014] Example 3:

[0015] In a 3L reaction vessel equipped with a stirrer, a thermometer, and a dropping funnel, add 500ml of 70% phosphoric acid solution and 1.2mol of p-toluidine (2). After dissolving, reduce the temperature of the solution to 6°C and add potassium sulfite 1.2mol of potassium sulfite solution prepared by dissolving in 300ml of water, controlling the reaction temperature to 18℃, after adding, continue to react for 15min, slowly adding 1.15mol of sodium iodate dissolved in 230ml of sodium iodate solution, controlling the temperature of the solution At 35°C, the stirring speed is controlled at 130rpm until the bubble generation speed in the reaction solution is slow, then adjust the solution temperature to 85°C, keep the temperature until no bubbles are generated, reduce the solution temperature to 30°C, pour the upper layer of liquid, and the remaining Add 0.3 mol of potassium nitrite to the oil to make the water layer colorless, add 300ml of 50% sodium carbonat...

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Abstract

A synthesis method of p-iodotoluene serving as a methotrexate drug intermediate comprises steps as follows: (i) 500 ml of a phosphoric acid solution with certain concentration and 1.2 mol of p-toluidine (2) are added to a 3L reaction container provided with a stirrer, a thermometer and a dropping funnel, the temperature of the solution is reduced to 3-6 DEG C after dissolution, 1.1-1.2 mol of potassium sulfite is added and dissolved in 300 ml of water, a potassium sulfite solution is prepared, the reaction temperature is controlled to be 15-18 DEG C, then, the mixture continuously reacts for 10-15 min, 1.1-1.15 mol of sodium iodate is slowly added and dissolved in 230 ml of water, a sodium iodate solution is prepared, the temperature of the solution is adjusted to be 80-85 DEG C, the solution is kept at the temperature until no bubbles are generated, the temperature of the solution is reduced to 25-30 DEG C, a supernatant liquid is poured out, 0.2-0.3 mol of potassium nitrite is added to remaining oily substances, a water layer is colorless, 300 ml of a sodium carbonate solution with certain concentration is added, the pH value of the solution is 8-9, water steam is distilled until no oily substances are distilled, the temperature of the solution is reduced to 5-8 DEG C, orange-yellow crystals are obtained, filtered, washed with a detergent and dewatered with a dewatering agent, and p-iodotoluene is obtained.

Description

technical field [0001] The invention relates to a method for synthesizing p-iodotoluene, a drug intermediate of methotrexate. Background technique [0002] Methotrexate is an anti-folate antineoplastic drug, which mainly inhibits the synthesis of tumor cells by inhibiting dihydrofolate reductase, thereby inhibiting the growth and reproduction of tumor cells. An important coenzyme for the synthesis of purine nucleotides and pyrimidine deoxynucleotides in the body, as a folate reductase inhibitor, it mainly inhibits dihydrofolate reductase so that dihydrofolate cannot be reduced into physiologically active tetrahydrofolate, thereby It hinders the transfer of one-carbon groups during the biosynthesis of purine nucleotides and pyrimidine nucleotides, resulting in the inhibition of DNA biosynthesis. In addition, this product also has an inhibitory effect on thymonucleotide synthetase, but its inhibitory effect on RNA and protein synthesis is relatively weak. This product mainly ...

Claims

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Application Information

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IPC IPC(8): C07C17/093C07C17/38C07C17/383C07C25/02
CPCC07C17/093C07C17/38C07C17/383
Inventor 彭响亮
Owner CHENGDU ZHONGHENG HUATIE TECH CO LTD
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