239463-72-0

Basic information

• Product Name: 5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole
• Synonyms: 5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole;5-(2-Aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate;(R)-3-(5-(2-aminopropyl)-7-cyanoindolin-1-yl)propyl benzoate(WXG00183)
• CAS NO: 239463-72-0
• Molecular Formula: C₂₂H₂₅N₃O₂
• Molecular Weight: 363.4528
• Mol File: 239463-72-0.mol

Chemical Properties

• Boiling Point: 567.4±50.0 °C(Predicted)
• Appearance: /
• Density: 1.20±0.1 g/cm3(Predicted)
• PKA: 9.65±0.10(Predicted)
• CAS DataBase Reference: 5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole(CAS DataBase Reference)
• NIST Chemistry Reference: 5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole(239463-72-0)
• EPA Substance Registry System: 5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole(239463-72-0)

Safety Data

• Hazardous Substances Data: 239463-72-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research:
5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole is used as a research compound for exploring its potential biological activities and therapeutic effects. Its unique structure allows scientists to investigate its interactions with various biological targets and pathways, potentially leading to the discovery of new drugs.
Used in Drug Development:
In the drug development industry, 5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole is utilized as a lead compound for the design and optimization of novel therapeutic agents. Its unique structural features can be further modified and fine-tuned to enhance its pharmacological properties, such as potency, selectivity, and bioavailability.
Used in Medicinal Chemistry:
5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole serves as a valuable tool in medicinal chemistry for the synthesis of new chemical entities and the study of structure-activity relationships. Its versatile molecular framework can be employed to design and synthesize a variety of analogs with potential therapeutic applications.
Used in Drug Discovery:
In the field of drug discovery, 5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole is employed as a starting point for the identification of new drug candidates. Its unique structural features can be exploited to screen and optimize compounds with desired pharmacological properties, ultimately leading to the development of innovative therapeutic agents.
Used in Chemical Biology:
5-[(2R)-2-Aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-carbonitrile-1H-indole is utilized in chemical biology as a probe to study the molecular mechanisms underlying various biological processes and diseases. Its interactions with specific targets can provide valuable insights into the underlying molecular pathways, facilitating the development of targeted therapeutic strategies.

Upstream product

• 496-15-1 1-indoline 
• 65-85-0 benzoic acid 
• 350797-53-4 1-(3-benzoyloxypropyl)-5-(2-nitro-1-propenyl)-2,3-dihydroindole 
• 350797-54-5 1-(3-benzoyloxypropyl)-5-(2-nitropropyl)-2,3-dihydroindole 
• 350797-55-6 1-(3-benzoyloxypropyl)-7-formyl-5-(2-nitropropyl)-2,3-dihydroindole 
• 350797-56-7 1-(3-benzoyloxypropyl)-7-cyano-5-(2-nitropropyl)-2,3-dihydroindole 
• 1338365-54-0 5-(2-aminopropyl)-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-cyano-1H-indole 
• 350797-51-2 1-(3-benzoyloxypropyl)-2,3-dihydroindole hydrochloride 
• 350797-52-3 1-(3-benzoyloxypropyl)-5-formyl-2,3-dihydroindole 
• 1402161-28-7 5-[2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-carbonitrile L-(+)-tartrate 
• 350797-57-8 C₂₂H₂₂N₂O₃ 
• 76699-29-1 1-(3-chloropropyl)indoline 

Downstream Products

• 885340-11-4 2,3-dihydro-1-[3-(benzoyloxy)propyl]-5-[(2R)-2-[[2-[(2,2,2-trifluoroethoxy)phenoxy]ethyl]amino]propyl]-1H-indole-7-carbonitrile 
• 160970-54-7 silodosin 
• 885340-13-6 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carbonitrile 
• 239463-85-5 5-[(2R)-2-aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-1H-indol-7-carbonitrile (2R,3R)-2,3-dihydroxybutanedioate salt 
• 1426173-86-5 C₂₅H₂₈⁽²⁾H₄F₃N₃O₄ 
• 885340-12-5 (2R)-3-(7-cyano-5-(2-((2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethyl)amino)propyl)-2,3-dihydro-1H-indol-1-yl)propyl benzoate oxalate 

Relevant articles and documents

5-substituted indoline derivative or salt thereof, preparation method and application of 5-substituted indoline derivative or salt thereof, and preparation method of silodosin

The invention relates to the technical field of medicines, in particular to a 5-substituted indoline derivative or a salt thereof, a preparation method and application of the 5-substituted indoline derivative or the salt thereof, and a preparation method of silodosin. Silodosin can be prepared by taking the 5-substituted indoline derivative provided by the invention as an intermediate through first N-alkylation, bromination, cyano substitution, deprotection, second N-alkylation and hydrolysis. The reaction route is short, and the total yield of the silodosin is high. The 5-substituted indoline derivative salt provided by the invention has good stability. According to the method, phthalic anhydride or substituted phthalic anhydride and D-alanine are taken as starting materials, the 5-substituted indoline derivative can be obtained through condensation, acylating chlorination, Friedel-Crafts reaction, reduction and hydrolysis, the reaction route is short, chiral construction does not need resolution, the atom utilization rate is high, the total yield is larger than 57.5%, and the yield is high; and the raw materials are cheap and easily available, and the production cost is low.

Preparation method of silodosin

The invention discloses a preparation method of silodosin. The preparation method comprises the following steps: S1, carrying out an asymmetric Henry condensation reaction on a substance 1 and nitroethane under the action of a copper salt and a chiral catalyst 2 to obtain a substance 3; S2, carrying out a reduction reaction on the substance 3 and hydrogen under the action of a catalyst 4 to obtaina substance 5; and S3, enabling the substance 5 to react with 2-(2-trifluoroethoxyphenoxy)ethyl methanesulfonate and an alkali to obtain a substance 6, and hydrolyzing the substance 6 to obtain silodosin. The method is novel in route, short in synthetic route, mild in reaction condition and convenient and controllable to operate, the chiral center is directly synthesized by the chiral catalyst without chiral resolution, and the prepared silodosin is good in chiral purity, high in yield, obvious in cost advantage and suitable for industrial production.

Preparation method of silodosin intermediate

The invention discloses a preparation method of a silodosin intermediate. The preparation method includes: allowing 5-bromoindoline solution and triethylamine to be in alkylation reaction to obtain asubstance A; allowing a solution of the substance A, ethyl acetoacetate, catalyst and acid-binding agent to be in substitution reaction to obtain a substance B; allowing a solution of the substance Band Lewis acid to be in decarboxylic reaction to obtain a substance C; allowing a solution of the substance C, R-tert butyl sulfonamide, catalyst and reducer to be in amination reaction to obtain a substance D; allowing a solution of the substance D and N-bromosuccinimide solution to be in bromination reaction to obtain a substance E; allowing a solution of the substance E and cuprous cyanide to be in cyanation reaction to obtain a substance F; allowing a solution of the substance F and acid to be in acidolysis reaction to obtain a substance G; preparing the substance G into tartrate to obtainthe silodosin intermediate. The preparation method is simple, high in yield, low in energy consumption and environment-friendly; the silodosin intermediate prepared by the method is high in quality and suitable for large-scale industrial production.

Improved synthetic method of (R)-1-aryl-2-propylamine

The invention provides an improved synthetic method of (R)-1-aryl-2-propylamine. The improved synthetic method comprises the following steps of: adopting 1-arylacetone as a raw material, adding (R)-1-phenylethylamine, carrying out reductive amination reaction with hydrogen under a common action of a Lewis acid additive and a transitional metal hydrogenation catalyst; carrying out Pd/C catalytic hydrogenation on an obtained intermediate to remove phenethyl on nitrogen and thus obtaining (R)-1-aryl-2-propylamine. The improved synthetic method provided by the invention has the beneficial effectsthat the operation is simple, the adopted Lewis acid additive is low in cost and easy in obtaining, the yield and the enantioselectivity of a product are high, and the application value for industrialsynthesis of (R)-1-aryl-2-propylamine is very high.

A process for preparing the silodosin intermediates

The invention discloses a preparation method of a silodosin intermediate, wherein the structure of the silodosin intermediate is represented as the formula A. The preparation method, wherein indoline is employed as a start raw material, includes the reactions of Friedel-Crafts acylation, carbonyl reduction, Gabriel reaction and chiral resolution and the like. The preparation method is simple in operation, is low in cost, is high in yield, allows the product to purify easily and is stable in processes, and is suitable for industrial production. The invention also discloses a new intermediate compound which is related in the method.

Method for preparing silodosin

The invention relates to a method for preparing silodosin, especially to an industrial preparation method of a silodosin compound, and belongs to the field of pharmaceutical chemical synthesis. The method includes: carrying out salt hydrolysis on 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-nitrile tartrate to obtain 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-nitrile, preparing benzoic acid-R-3-[7-cyano-5-(2-{2-[2-(2,2,2-trifluoro-ethoxy)-phenoxyl]-ethylamino}-propyl)-2,3-dihydro-indole-1-yl]-propylester which is an intermediate, and finally performing a hydrolysis reaction to produce silodosin. According to the provided industrial production method of silodosin, the yield is high, purification becomes easy and the impurity content is low.

Synthesis of silodosin glucuronide and its deuterated counterpart: Solving a problematic O-glycosylation of a nitrogen-containing molecule

We report here the first chemical synthesis of silodosin glucuronide, a metabolite of the α1A-adrenoceptor antagonist silodosin, and its deuterium-labeled counterpart. As a key synthetic step, the incorporation of a glucuronosyl unit onto silodosin invariably led to either an undesired orthoester or a complex mixture under an array of standard glycosylation conditions. This problematic O-glycosylation may be attributed to the presence of multiple basic groups that could neutralize the acidic activators, decrease the nucleophilicity of a hydroxy group via hydrogen bond or even facilitate acyl migration side reactions. After elaborate tuning of reaction conditions, success was eventually achieved by using perbenzoylated d-glucuronosyl N-phenyltrifluroacetimidate (PTFA) as donor in combination with a procedure of sequential addition of TMSOTf. This protocol is potentially general for the glycosylation of other nitrogen-containing small molecule drugs.

Preparation method of indoline derivative for synthesizing silodosin

The invention provides a preparation method of an indoline derivative for synthesizing silodosin. Indoline is taken as a starting raw material and reacts with benzoic acid and 1-chloro-3-bromopropane to prepare a compound (1); a reaction is carried out in a Vilsmeier agent, and a formyl group in introduced to the 5th position to prepare a compound (2); the compound (2) and nitroethane undergoes an asymmetric Henry reaction in the catalysis of quinidine-copper acetate to prepare a compound (3); the compound (3) is subjected to acetylation through acetic anhydride to prepare a compound (4); a cyano group is introduced to the 7th position to prepare a compound (6); and two functional groups are reduced through palladium-on-carbon hydrogenation in one step to obtain a high-chiral-purity target compound: (R)-1-[1-(3-benzoyloxypropyl)-5-(2-aminopropyl)-7-cyano]indoline. In the early stage of the method, cheap quinidine is used to perform an asymmetric Henry reaction for introduction of chiral centers, thereby avoiding resolution in the latter stage. The method is reasonable in design, simple to operate, effectively improved in yield and reduced in cost, and therefore is suitable for massive production.

Preparation method of intermediate for synthesis of silodosin

The invention provides a preparation method of an intermediate for synthesis of silodosin. The preparation method comprises that indoline as a starting material, benzoic acid and 1-chloro-3-bromopropane undergo a reaction so that a benzoyloxypropyl group is introduced to the 1th site of indoline and a compound I is obtained, the compound I and L-lactic acid undergo a reaction to produce a compound II, the compound II undergoes a Friedel-Crafts acylation reaction so that a chiral center is introduced and a compound III is obtained, a compound V is prepared through carbonyl reduction and inversion of configuration, a cyano group is introduced into the 7th site of the compound V so that a compound VII is obtained, and the nitro group is reduced so that a desired compound with high chiral purity is obtained and is (R)-1-[1-(3-benzoyloxypropyl)-5-(2-aminopropyl)-7-cyano]indoline. The preparation method introduces a chiral center through cheap lactic acid in the early stage of the route, prevents the later resolution, has a reasonable design, can be operated simply, effectively improves a yield, reduces a cost and is suitable for large-scale production.