Synthesis method of p-iodotoluene serving as methotrexate drug intermediate

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 ...

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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 mainly acts on the S phase of the cell cycle, and is a cell cycle-specific drug. The cells in the phase also have a delaying effect, and the effect on the cells in the G1 phase is weak

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