- Nilotinib hydrochloride bulk drug impurity and preparation method thereof
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The invention provides a preparation method of a nilotinib hydrochloride bulk drug impurity. The preparation method comprises the following steps: S1) reducing a compound as shown in a formula (II) to obtain a compound as shown in a formula (III); and S2) subjecting the compound as shown in the formula (III) to reacting with imidazole to obtain the nilotinib hydrochloride bulk drug impurity as shown in the formula (I). The formulas are as defined in the specification, and X in the formulas is halogen. Compared with the prior art, the preparation method of the impurity in the initial raw material of nilotinib hydrochloride provided by the invention has the advantages that raw materials are easy to obtain, a process route is relatively short, precious metals such as palladium can be prevented from being used for a reaction, quinoline compounds are not used, and residues of the quinoline compounds are avoided; and the method can be used for process development, production, quality standard establishment and quality control links of nilotinib, and provides technical support for the medication safety of the monohydrate nilotinib hydrochloride.
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Paragraph 0039; 0048-0050; 0055-0057; 0060-0062; 0065-0067
(2021/05/12)
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- An efficient d-glucosamine-based copper catalyst for C-X couplings and its application in the synthesis of nilotinib intermediate
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d-Glucosamine has been studied for C-N and C-S bond formations via cross-coupling reactions of nitrogen and sulfur nucleophiles with both aryl iodides and bromides. Imidazoles, benzimidazole, indole, pyrrolidine and diphenyl disulfide undergo reactions with aryl halides in the presence of 10 mol% d-glucosamine, 10 mol% CuI, and 2 equiv. of Cs2CO3 in DMSO-H2O at moderate temperature to give the corresponding products in good to excellent yields. Substrates bearing halides, free amino groups, trifluoromethyl and heterocycles were well tolerated. The high water solubility of the ligand enables easy catalyst removal. In addition, the application of this catalytic system for the synthesis of nilotinib intermediate was also successfully demonstrated using commercially available substrates. This journal is
- Wen, Ming,Shen, Chao,Wang, Linfang,Zhang, Pengfei,Jin, Jianzhong
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p. 1522 - 1528
(2015/02/18)
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