- Refining method of quetiapine fumarate
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The invention provides a refining method of quetiapine hemifumarate. The refining method comprises the following steps: feeding crude quetiapine hemifumarate in a refining solvent, adding certain amount of fumaric acid, performing backflow pulping, cooling, crystallizing, filtering and drying to obtain a finished quetiapine hemifumarate product. Through adding the certain amount of fumaric acid, the refining yield and the refining efficiency can be respectively and effectively increased and improved. The invention further provides an impurity synthesis method.
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Paragraph 0028-0031
(2021/01/29)
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- Identification, isolation, synthesis and characterization of impurities of quetiapine fumarate
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In the process for the preparation of quetiapine fumarate (1), six unknown impurities and one known impurity (intermediate) were identified ranging from 0.05-0.15% by reverse-phase HPLC. These impurities were isolated from crude samples using reverse-phase preparative HPLC. Based on the spectral data, the impurities were characterized as 2-[4-dibenzo[b,f][1,4]thiazepine-11-yl-1- piperazinyl]1-2-ethanol (impurity I, desethanol quetiapine), 11-[(N-formyl)-1-piperazinyl]-dibenzo[b,f][1,4]thiazepine (impurity II, N-formyl piperazinyl thiazepine), 2-(2-hydroxy ethoxy)ethyl-2-[2-[4-dibenzo[b,f][1,4] thiazepine-11-piperazinyl-1-carboxylate (impurity III, quetiapine carboxylate), 11-[4-ethyl-1-piperazinyl]dibenzo [b,f][1,4] thiazepine (impurity IV, ethylpiperazinyl thiazepine), 2-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1- piperazinyl)ethoxy]1-ethyl ethanol [impurity V, ethyl quetiapine), 1,4-bis[dibenzo[b,f][1,4]thiazepine-11-yl] piperazine [impurity VI, bis(dibenzo)piperazine]. The known impurity was an intermediate, 11-piperazinyl-dibenzo [b,f][1,4]thiazepine (piperazinyl thiazepine). The structures were established unambiguously by independent synthesis and co-injection in HPLC to confirm the retention times. To the best of our knowledge, these impurities have not been reported before. Structural elucidation of all impurities by spectral data (1H NMR, 13C NMR, MS and IR), synthesis and formation of these impurities are discussed in detail.
- Bharathi,Prabahar,Prasad,Srinivasa Rao,Trinadhachary,Handa,Dandala, Ramesh,Naidu
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