- THE MANUFACTURING METHOD OF INTERMEDIATE FOR SYNTHESIS OF SILODOSIN AND THE MANUFACTURING METHOD OF SILODOSIN
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The present invention relates to a method for producing an intermediate for the synthesis, of a cilodosin, and a method for producing, a cilodosin using the, same, which can be used in a method for producing a cilodosin, which can increase the price competitiveness and can reduce. risk factors in the production process, facilitate mass production, and obtain a high purity of xylodosin. (by machine translation)
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- Preparation method of silodosin intermediate
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The invention discloses a preparation method of a silodosin intermediate and relates to the technical field of medical synthesis, aiming at solving the problem in an existing preparation method that the yield of the silodosin intermediate is low. The preparation method of the silodosin intermediate comprises the following steps: carrying out chirally-induced reductive amination on an alpha-substituted acetone compound to obtain an initial intermediate; carrying out amino protection on the initial intermediate to obtain an amino protected intermediate; carrying out hydroformylation on the aminoprotected intermediate to obtain a hydroformylated intermediate; carrying out oximation on the hydroformylated intermediate to obtain an oximated intermediate; carrying out cyaniding on the oximatedintermediate to obtain a cyanated intermediate; carrying out amino deprotection on the cyanated intermediate to obtain free alkali of the silodosin intermediate; carrying out salt forming treatment onthe free alkali of the silodosin intermediate to obtain the silodosin intermediate. The preparation method of the silodosin intermediate, provided by the invention, is used for preparing silodosin.
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- Method for preparing silodosin intermediate
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The invention discloses a method for preparing silodosin intermediate 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indolyl-7-nitrily-L-(+)-tartrate. The method specifically comprisesthe steps of recovering waste filter liquor in a resolution reaction, subjecting the filter liquor to catalyzed racemation by a palladium catalyst so as to prepare a raw material, i.e., 5-[2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indolyl-7-nitrile, and then, at least repeating resolution once, thereby increasing the yield of the resolution product, i.e., a key intermediate of silodosin, i.e., 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indolyl-7-nitrily-L-(+)-tartrate. The target product prepared by the method disclosed by the invention is high in yield and low in cost, preconceptions in the prior art are overcome, and thus, the method is more applicable to industrial production.
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Paragraph 0039; 0049; 0058; 0067; 0076; 0084; 0085
(2019/01/06)
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- Process for Production of Optically Active Indoline Derivatives or Salts Thereof
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The present invention relates to a synthesis method of optically active indoline derivatives or salts thereof, which are represented by general formula I and useful as a starting material for the production of drugs. By introducing terephthaloyl chloride as a starting material and using the same as a link in the synthesis of indoline derivatives or salts thereof, the present invention increases efficiency, greatly facilitates confirmation of intermediates, purification, and processes, and also increases the efficiency of reaction due to excellent stability. By using inexpensive and easy-to-handle zinc instead of expensive platinum catalyst, the present invention improves the yield thereof. By introducing a benzyl group into an amine group (general formula III, preferably chemical formula 23) to ensure optical purity in the final process, the present invention can produce, merely by means of recrystallization, optically pure indoline derivatives or salts thereof, represented by the general formula I.COPYRIGHT KIPO 2016
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Paragraph 0123; 0159; 0160; 0162; 0164; 0166
(2018/03/01)
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- Method for preparing silodosin midbody
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The invention discloses a method for preparing a silodosin midbody. The silodosin midbody is the compound shown in the formula (1) and prepared with indoline derivative and R-alanine derivative which are easy to obtain as starting materials through Friedel-Crafts acylation reaction, reduction reaction, formylation reaction, oximation reaction, dehydration reaction, hydrolysis reaction and salt forming reaction. The compound is used for preparing silodosin. Silodosin is used for treating urination disorder related to benign prostatic hyperplasia. The method has the advantages that raw materials are cheap and easy to obtain, operation is easy, yield is high, production cost is reduced, and the method is suitable for large-scale industrial production.
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- Design, Synthesis, and Biological Evaluation of Indoline and Indole Derivatives as Potent and Selective α1A-Adrenoceptor Antagonists
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A series of indoline and indole derivatives were designed, synthesized, and evaluated as selective α1A-adrenergic receptor (α1A-AR) antagonists for the treatment of benign prostatic hyperplasia (BPH). In this study, two highly selective and potent α1A-AR antagonists, compounds (R)-14r (IC50 = 2.7 nM, α1B/α1A = 640.1, α1D/α1A = 408.2) and (R)-23l (IC50 = 1.9 nM, α1B/α1A = 1506, α1D/α1A = 249.6), which exhibited similar activities and better selectivities in cell-based calcium assays as compared with the marketed drug silodosin (IC50 = 1.9 nM, α1B/α1A = 285.9, α1D/α1A = 14.4), were identified. In the functional assays with isolated rat tissues, compounds (R)-14r and (R)-23l also showed high potency and uroselectivity. Most importantly, (R)-14r and (R)-23l can significantly decrease the micturition frequency and increase the mean voided volume of the BPH rats in a dose-dependent manner, making them worthy of further investigation for the development of anti-BPH agents.
- Zhao, Fei,Li, Jing,Chen, Ying,Tian, Yanxin,Wu, Chenglin,Xie, Yanan,Zhou, Yu,Wang, Jiang,Xie, Xin,Liu, Hong
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p. 3826 - 3839
(2016/05/24)
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- METHOD FOR PREPARING SILODOSIN
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The present invention relates to a process for preparing silodosin with high optical purity up to 99.9% enantiomeric excess (e.e.) or above. The process makes use of a method step, in which the enantiomers contained in a racemic mixture of a compound represented by the general formula V: wherein * denotes the asymmetric center, R1 is a protecting group, and R2 is cyano or carbamoyl, are separated.
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- NOVEL PROCESS FOR THE SYNTHESIS OF INDOLINE DERIVATIVES
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The present invention provides an improved process for the synthesis of indoline intermidiate and its pharmaceutically acceptable derivatives, salts or solvates thereof, useful in the synthesis of α-1 adrenoceptor blockers such as silodosin.
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