CAS number：302962-49-8
molecular formula：C22H26ClN7O2S
molecular weight：488.01
EINECS number：801-607-0

English synonyms

SPRYCEL;BMS354825;DASATINIB (BMS 354825);CS-1968;N-(2-chloro-6-Methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-Methyl-4-pyriMidinyl]aMino]-1,3-thiazole-5-carboxaMide;sprycel Dasatinib;BMS-354825; SPRYCEL;25MG/100MG/1G;NCGC00181129;Dasatinib (Dasatinib Monohydrate) Tablet

Related categories

Pharmaceutical intermediates; scientific research reagents; medical raw materials; cell biology reagents; scientific research products - self-developed spot products; medical raw materials; angiogenesis; small molecule inhibitors, natural products; raw materials (CPI); Dasatinib, Dasatinib; APIs; signal transduction pathway kinase inhibitors; intermediates; anti-cancer; pharmaceutical raw materials; small molecule inhibitors; Drug Impurities-Dasatinib; APIs and intermediates; Chemical raw materials; Chemical raw materials; Intermediates & Fine Chemicals; Pharmaceuticals; Tyrosine Kinase Inhibitors; Pharmaceutical intermediate; Inhibitor; Sprycel; Anti-cancer&immunity; agent

Introduction

Dasatinib, also known as Sprycel, is an off-white to yellow solid chemical. Chemical name N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl ]Amino]-5-thiazole carboxamide, dasatinib is an antineoplastic drug, and it mainly treats imatinib mesylate resistance or intolerant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia ( CML) adult patients in chronic phase, accelerated phase and blast phase (acute myeloid change and acute lymphoblastic change).

Chemical properties

Use

●  It is suitable for chronic myeloid leukemia that is resistant or intolerant to treatment regimens including imatinib mesylate

●  This product is used for the treatment of imatinib mesylate resistance, or intolerant Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) chronic phase, accelerated phase and blast phase (acute myeloid change and acute lymphoblastic change ) adult patients.

●  Dasatinib is a protein kinase inhibitor that can inhibit BCR-ABL kinases and SRC family kinases as well as many other selective oncogenic kinases, including c-KIT, ephrin (EPH) receptor kinases and PDGFβ receptors. Adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) who are resistant to or intolerant of imatinib mesylate in chronic phase, accelerated phase, and blast phase (accelerated myeloid change and acute lymphoblastic change).

Production method

A preparation method of dasatinib, comprising the following steps:
●  Preparation of N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methyl-4-pyrimidinyl)amino]-5-thiazole carboxamide: at room temperature, the 1.50kg 2-amino-N-(2-chloro-6-methylphenyl)-5-thiazole amide, 1.11kg 4,6-dichloro-2-methylpyrimidine were added to the 50L reaction kettle, and 13.35kg Tetrahydrofuran, nitrogen protection, stirring to cool down to -5 ° C ~ 10 ° C, the temperature of the reaction solution is maintained at -5 ° C ~ 10 ° C, adding sodium tert-butoxide solids to the reaction solution in stages, the total amount of sodium tert-butoxide solids is 2.13 kg, the addition method is to add once every 20-30min, each time no more than 10% of the total amount and no more than 200g at most. After the solution, the temperature was raised to 10°C to 30°C, and the reaction liquid was stirred until the HPLC detection of 2-amino-N-(2-chloro-6-methylphenyl)-5-thiazole amide/N-(2-chloro-6- The amount of methylphenyl)-2-[(6-chloro-2-methyl-4-pyrimidinyl)amino]-5-thiazole carboxamide is less than 1.5%, and the reaction solution is cooled to -10°C to 10°C , dropwise add hydrochloric acid with a concentration of 4mol/L, adjust the pH of the system to 6~7, continue to stir at -10°C~10°C for 1~2h after the dropwise addition, filter, wash the filter cake with an appropriate amount of water and methanol, and wash the filter cake in Vacuum drying at 50-60°C to obtain N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methyl-4-pyrimidinyl)amino]-5-thiazolecarboxamide 1.636 kg, yield 74.06%;
●  Preparation of crude dasatinib: at room temperature, 1.60kg of N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methyl- 4-pyrimidinyl)amino]-5-thiazolecarboxamide, 1.056kgN-hydroxyethylpiperazine, 0.432kg triethylamine were added to a 50L reaction kettle, 5.60kg N-methylpyrrolidone was added, under nitrogen protection, the reaction solution was stirred Raise the temperature to 70-75 °C, continue to stir, wait for HPLC to detect N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methyl-4-pyrimidinyl)amino]-5 - When the amount of thiazole carboxamide/dasatinib is lower than 0.5%, start to cool down to 15-30°C, add 22.4kg of dichloromethane, stir for 0.5-1.0h, filter the material, and use an appropriate amount of dichloromethane to filter the obtained filter cake Wash with methane, vacuum dry at 50-60°C for 4-6 hours, put the dried filter cake into the reactor, add 5.60kg of N-methylpyrrolidone, heat up to 35-45°C and stir to dissolve, filter the material, and put the obtained filtrate into the reactor. After adding 19.2kg of dichloromethane under stirring, lower the temperature to 15-30°C and stir for 0.5-1.0h, filter the material, rinse the obtained filter cake with an appropriate amount of dichloromethane, and vacuum-dry at 50-60°C to obtain crude dasatinib 1.9 kg, yield 96%;
●  Refined dasatinib: Add 1.90kg of the crude dasatinib obtained in step (2) and 45.0kg of anhydrous methanol into the reaction kettle, stir, replace with nitrogen, heat up to reflux while stirring, and then stir for 1 to 2 hours , lower the temperature to 59-63°C, add seed crystals, and stir at 59-63°C for 0.5-1h, then adopt a uniform cooling method to cool down, and cool down by 2-5°C every 10min, after the temperature drops to 5-10°C, keep the temperature Stir for 0.5-1h, filter the material, rinse the obtained filter cake with an appropriate amount of methanol, and then dry the filter cake in a gradient temperature-raising manner. First, dry the filter cake at 38-42°C until the filter cake has a constant weight, and then heat it up to 48-52°C under vacuum. Dry to a constant weight of the filter cake, and finally heat up to 76-80°C and vacuum dry to a constant weight of the filter cake to obtain 1.252 kg of the final product of dasatinib, with a yield of 65.9%, and the impurity content detected by HPLC is less than 0.1%.

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