231278-84-5Relevant articles and documents
Preparation method of 6-substituted furanyl-4-substituted aminoquinazoline derivative and key intermediate thereof
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, (2020/02/14)
The invention relates to a preparation method of a 6-substituted furanyl-4-substituted aminoquinazoline derivative and a key intermediate thereof. 2-halo-5-cyanobenzoate and 3-chloro-4-(3-fluorobenzyloxy)aniline are used as raw materials, and 6-cyano-4-[3-chloro-4-(3-fluorobenzyloxy)phenyl]aminoquinazoline is obtain through an amidation reaction, a formamidine salt substitution reaction and a condensation reaction; then 6-(furan-2-yl)-4-[3-chloro-4-(3-fluorobenzyloxy)phenyl]aminoquinazoline or 6-(5-formylfuran-2-yl)-4-[3-chloro-4-(3-fluorobenzyloxy)phenyl]aminoquinazoline are obtained througha Grignard reaction and an acidification reaction; and then lapatinib or selatinib are prepared through a Mannich reaction or imidization and a reductive amination reaction. The preparation method hasthe advantages that the raw materials are cheap and are easily available, selectivity of the reaction is high, purity of the product is high, and industrial production is facilitated.
A high-purity paratoluene sulfonic acid lapatinib a preparation method of water composition
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Paragraph 0019, (2019/04/04)
The invention relates to a high-purity paratoluene sulfonic acid lapatinib a water composition of the preparation method, the method comprises the following steps: (1) the compound II with compound III under alkaline conditions, the catalyst under the action of the Suzuki coupling to obtain compound IV; (2) the compound IV with a compound V in weakly alkaline conditions, in the catalyst under the action of the joint, by the three-b acyl sodium borohydride reduction, paratoluene sulfonic acid to form the salt to obtain compound VI; (3) the compound VI with the recrystallization to obtain compound I, is the second-to-toluene sulfonic acid lapatinib a hydrate. The programme provides at least to a certain extent one of the solve the above technical problems or at least provide a useful commercial choice. To avoid the use of toxicity is relatively high, the environmentally harmful solvent or reagent, the reaction route is operating time is short, the reaction system is stable, the purification process is simple, the product purity is higher, it is suitable for industrial production.
Synthesis and in vitro biological evaluation of novel quinazoline derivatives
Zhang, Yaling,Zhang, Ying,Liu, Juan,Chen, Li,Zhao, Lijun,Li, Baolin,Wang, Wei
supporting information, p. 1584 - 1587 (2017/03/16)
A series of novel 4-arylamino-6-(5-substituted furan-2-yl)quinazoline derivatives were designed, synthesized and evaluated on biological activities in vitro. Compound 2a, 3a and 3c exhibited highly anti-proliferation activities on all tested tumor cell lines including SW480, A549, A431 and NCI-H1975 cells. Especially, compound 2a not only exhibited strong anti-proliferation activities against the tumor cell lines which expressed wild type or mutant EGFRL858R/T790M, but also showed the most potent inhibitory activity toward wild type EGFR (IC50?=?5.06?nM). The result of docking with EGFR suggested the binding mode of 2a was similar to that of lapatinib. While Western-blot analyses showed 2a obviously inhibited the activation of EGFR, Akt and Erk1/2 in lung cancer cells at indicated concentration. It is believed that this work would be very useful for developing a new series of TKIs targeting EGFR.
