Molecular Formula | C22H20ClN3O4 |
Molar Mass | 425.86 |
Density | 1.429±0.06 g/cm3(Predicted) |
Boling Point | 720.5±60.0 °C(Predicted) |
Storage Condition | 2-8°C |
Wu Puhua ,< a href = "https://xueshu.baidu.com/usercenter/data/author?cmd=authoruri&wd=authoruri:(350 a30f07caf8920) author:(Liao Lin)" target = "_blank"> Liao Lin ,< a href = "https://xueshu.baidu.com/usercenter/data/author?cmd=authoruri&wd=authoruri:(23 fd7ac47eb0da09) author:(Xie Yipeng)" target = "_blank"> Xie Peng
Summary:
Objective In order to strengthen the quality control of tadalafil and its intermediates, four new impurities of tadalafil were synthesized. Methods (1R,3R)-1-(1,3-benzodioxolane -5-yl)-1,2,3,4-tetrahydro-9H-pyridino [3,4-b] indole -3-carboxylate methyl ester hydrochloride was used as starting material, and the key intermediates 6a,6b were prepared by hydrolysis, Boc anhydride protection, benzyl ester protection reaction, acid catalysis removal, impurities I1 and I2 were synthesized by acylation and hydrogenation debenzylation of the intermediate respectively. I2 and I2 are synthesized by nucleophilic substitution reaction to obtain impurities Ⅱ 2 and Ⅱ 2. Results and conclusion the structures of the four kinds of impurities and their intermediates were confirmed by NMR and MS spectra. the purity of the four kinds of impurities reached more than 96%, which can be used as impurity reference substance for tadalafil quality control.
keywords:
DOI:
CNKI:SUN:ZGYH. 0.2017-03-008
Year:
2017
CN201811649077.6
date of application:
2018-12-30
public/announcement number:
CN109796461A
date of publication/announcement:
2019.05.24
Applicant (patentee):
Hangzhou Koben Pharmaceutical Technology Co., Ltd.; Hangzhou Koben Pharmaceutical Research Co., Ltd.; Jiangsu Koben Pharmaceutical Co., Ltd.
Inventor:
Shi lei , you jinzong , Jiang Shanhui
national and provincial code:
CN330110
Summary:
The present invention discloses a preparation process of tadalafil impurity I, which includes the following steps:(1) mixing tadalafil, N halosuccinimide and a solvent in a reaction container, stirring at 2050°C for reaction, TLC tracking reaction, the solvent is selected from one or more combinations of tetrahydrofuran, water, and glacial acetic acid, one or a combination of N iodosuccinimide;(2) After stopping the reaction, slowly add lye to the reaction solution until the solution pH ≥ 7, stir for 20-60min, evaporate the organic solvent under reduced pressure, dichloromethane extracts the remaining aqueous solution, and the extract is concentrated to obtain a crude product, the reaction conditions are mild, the operation is simple, and the purity of the obtained tadalafil impurity I is good and meets the requirements of the Pharmacopoeia.