139756-03-9

Basic information

• Product Name: 4-(2-Ethoxy benzamido)-1-methyl-3-n-propyl pyrazole-5-carboxamide.
• Synonyms: 4-(2-Ethoxy benzamido)-1-methyl-3-n-propyl pyrazole-5-carboxamide.;Sildenafil CarboxaMide IMpurity;4-[(2-Ethoxybenzoyl)aMino]-1-Methyl-3-propyl-;Sildenafil Di-AMide IMpurity;4-(2-Ethoxybenzamido)-1-methyl-3-propyl-1H-pyrazole-5-carboxamide
• CAS NO: 139756-03-9
• Molecular Formula: C₁₇H₂₂N₄O₃
• Molecular Weight: 330.38158
• Product Categories: Sildenafil Citrate;Heterocycles;Impurities;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 139756-03-9.mol

Chemical Properties

• Melting Point: 153-155 °C
• Boiling Point: 445.5°C at 760 mmHg
• Flash Point: 223.2°C
• Appearance: /
• Density: 1.24g/cm³
• Vapor Pressure: 3.94E-08mmHg at 25°C
• Refractive Index: 1.598
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 12.65±0.70(Predicted)
• CAS DataBase Reference: 4-(2-Ethoxy benzamido)-1-methyl-3-n-propyl pyrazole-5-carboxamide.(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(2-Ethoxy benzamido)-1-methyl-3-n-propyl pyrazole-5-carboxamide.(139756-03-9)
• EPA Substance Registry System: 4-(2-Ethoxy benzamido)-1-methyl-3-n-propyl pyrazole-5-carboxamide.(139756-03-9)

Safety Data

• Hazardous Substances Data: 139756-03-9(Hazardous Substances Data)

Usage

Uses

An impurity of Sildenafil (S435000) (impurity C).

InChI:InChI=1/C17H22N4O3/c1-4-8-12-14(15(16(18)22)21(3)20-12)19-17(23)11-9-6-7-10-13(11)24-5-2/h6-7,9-10H,4-5,8H2,1-3H3,(H2,18,22)(H,19,23)

Upstream product

• 54090-36-7 2-propoxybenzoyl chloride 
• 134-11-2 2-ethoxybenzoic acid 
• 139756-02-8 4-amino-1-methyl-3-propyl-1H-pyrazole-5-carboxamide 
• 304435-83-4 4-amino-2-methyl-5-propyl-2H-pyrazole-3-carboxylic acid ethyl ester 
• 1023327-67-4 4-amino-4,5-dihydro-1-methyl-3-propyl-1H-pyrazole-5-carboxamide 
• 42926-52-3 2-ethoxybenzoyl chloride 
• 139756-00-6 1-methyl-2-nitro-3-propyl-1H-pyrazole-5-carboxylic acid 
• 133261-07-1 1-Methyl-3-n-propylpyrazole-5-carboxylic acid ethyl ester 
• 139755-99-0 1-methyl-3-propyl-1 H-pyrazole-5-carboxylic acid 
• 36983-31-0 ethyl 3-butyrylpyruvate 
• 139756-01-7 1-methyl-4-nitro-3-propyl-1H-pyrazole-5-carboxamide 
• 865855-32-9 4-bromo-1-methyl-3-propyl-1H-pyrazole-5-carboxamide 
• 938-73-8 2-ethoxybenzamide 

Downstream Products

• 139755-83-2 sildenafil 
• 171599-83-0 sildenafil citrate 
• 139756-22-2 5-(5-Chlorosulphonyl-2-ethoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 
• 147677-00-7 5-(5-amino-2-ethoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]-pyrimidin-7-one 
• 1033861-31-2 7-chloro-1-methyl-5-[2-ethoxy-5-(chlorosulfonyl)phenyl]-3-n-propyl-1H-pyrazolo[4,3-d]pyrimidine 
• 946856-58-2 5-[2-ethoxyphenyl]-1-methyl-7-chloro-3-propyl-1H-pyrazolo[4,3-d]pyrimidine 
• 139755-85-4 5-[2-ethoxy-5-[4-(2-hydroxyethyl)-1-piperazinyl-sulphonyl]phenyl}-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 
• 139755-83-2 viagra 
• 374776-41-7 4-(2-ethoxy-5-(4-(3-ethoxycarbonylpropyl)piperidinylsulfonyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carboxamide 
• 374776-45-1 4-(2-ethoxy-5-(4-(2-ethoxycarbonylethyl)piperazinylsulfonyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carboxamide 
• 374776-39-3 4-(2-ethoxy-5-(4-(2-ethoxycarbonylethyl)piperidinylsulfonyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carboxamide 
• 374776-43-9 4-(2-ethoxy-5-(4-(ethoxycarbonylmethyl)piperazinylsulfonyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carboxamide 
• 374776-37-1 4-(2-ethoxy-5-(4-(ethoxycarbonylmethyl)piperidinylsulfonyl)benzamido)-1-methyl-3-n-propylpyrazole-5-carboxamide 

Relevant articles and documents

Improved synthesis process of sildenafil

The invention discloses an improved synthesis process of sildenafil, belonging to the technical field of preparation of drug intermediates. In the process, high-concentration chlorosulfonic acid is prevented from being used as a reaction solvent and reagent, and 3-5 equivalent chlorosulfonic acid is used as a reaction reagent. Compared with the prior art, the process has the characteristics of economical performance, environmental protection, safety and the like, for example, equipment cannot be corroded, the post-treatment of reaction becomes simpler, the solvent is single and can be reused, product purity is high, and the like.

Method for preparing sildenafil citrate

The invention discloses a method for preparing sildenafil citrate. The preparation method comprises the following steps: (a) adding a compound II into chlorosulfonic acid for a reaction to generate anintermediate III; (b) reacting the intermediate III with N-methyl piperazine to generate a crude sildenafil product; (c) recrystallizing the crude sildenafil product to obtain a pure sildenafil product; and (d) carrying out a salifying reaction on the pure sildenafil product to obtain sildenafil citrate. The method is beneficial for industrial production.

Preparation method of sildenafil

The invention provides a preparation method of sildenafil. The preparation method comprises the following steps: dissolving a compound III in an organic solvent I, adding a compound II for amidation reaction, washing and drying to obtain a compound IV; directly adding the solution obtained in the step S1 into a chlorosulfonic acid-thionyl chloride mixture for chlorosulfonation reaction without separation and purification, pouring ice water after the reaction is finished, layering, taking an organic phase, washing and drying to obtain a compound V; adding the compound V obtained in the S2 intoN-methyl piperazine, carrying out N-sulfonation reaction for 0-4 hours, concentrating, adding alkali and an organic solvent II, heating to carry out cyclization reaction for 2-6 hours, adding water for cooling, adding hydrochloric acid for acidification, and filtering to obtain a target compound I. A continuous method is adopted for synthesis, and the production efficiency is improved.

Sildenafil intermediate synthesis method

Sildenafil has a good effect of treating male erectile dysfunction (ED) in clinic. Many preparation methods of sildenafil have been already reported and mostly belong to two-step synthesis. The two-step post-treatment operation is relatively tedious, and yield is low. The invention provides a synthesis method of a sildenafil intermediate, comprising the following steps: dissolving a compound II inan organic aprotic solvent, and adding a compound I to carry out a condensation reaction; adding alkali to carry out a cyclization reaction after it is monitored that the compound II is completely reacted so as to obtain a compound IV. By ''one-pot'' synthesis, generation of ''three wastes (waste gas, waste water and industrial residue)'' is reduced, reaction time is greatly shortened, reaction yield is raised, and stability is good.

Preparation method of sildenafil citrate

The invention belongs to the field of chemical drugs, and in particular relates to a preparation method of sildenafil citrate. The invention provides the preparation method of sildenafil citrate. Thepreparation method comprises the following steps: a) adding a compound of a structure as shown in a formula (I) and thionyl chloride into chlorosulfonic acid, and carrying out a sulfonation reaction to generate a compound of a structure as shown in a formula (II); b) dissolving the compound of the structure as shown in the formula (II) in dichloromethane and adding N-methyl piperazine to carry outa substitution reaction at 20-30 DEG C to obtain sildenafil; and c) adding citric acid into a sildenafil aqueous solution to adjust the pH value for a salt forming reaction so as to obtain the sildenafil citrate. Experimental results verify that the sildenafil citrate prepared by the preparation method is high in yield and high in purity.

Sedinafine derivatives of the microwave-assisted method for preparing

The invention discloses a microwave-assisted synthesis method of sildenafil derivatives, which mainly comprises the following steps: by using 2-alkoxybenzoic acid and 4-amino-1-methyl-3-n-propyl-1H-pyrazolyl-5-formamide as initial raw materials, carrying out amidation, cyclization, mononitration, nitro reduction, guanidylation and the like to obtain the sildenafil derivatives. The method greatly shortens the reaction time, enhances the reaction efficiency, has the advantages of high yield and high purity, is simple to operate and easy to control, and is beneficial to industrial production of sildenafil analogs.

Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. Part 1. Sildenafil analogs

Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and well-being in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this Letter we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors.

Liquid-chromatography determination of impurities in sildenafil citrate

A simple, economic and time-efficient stability-indicating, reversed phase liquid chromatographic (RP-LC) method has been developed for the analysis of sildenafil citrate in the presence of both process related impurities and degradation products generated by decomposition. The drug was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. Considerable degradation was found to occur in alkali and oxidative stress conditions. The drug was found to be stable to other stress conditions attempted. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.6 %. The method was validated with respect to specificity, linearity, accuracy, precision, robustness, limit of detection and quantification. The method is simple, rapid, selective, accurate and stability indicating, useful in the quality control of bulk manufacturing of sildenafil.

PROCESS FOR THE PREPARATION OF SILDENAFIL AND INTERMEDIATES THEREOF

The present invention discloses a process for preparing sildenafil and its intermediates having the structures outlined below: In particular, the present invention provides a process for preparing the compound of formula (I) and its intermediates, i.e. the compounds of formula (I), (II), (III) and (IV). The compound of formula (I) is obtained from the compound of formula (II); the compound (II) is obtained from the compound of formula (III) and methylpiperazine; the compound (III) is obtained by treating the compound of formula (IV) with chlorosulfonic acid; the compound (IV) is obtained though treating the compound of formula (V) in the presence of at least one selected from POX3, PX3, PX5 and their mixtures in any ratio. The process for preparing the compound of formula (I) according to the present invention reduces the side reactions in the processes of the prior art. These improvements lead to higher yields and a better industrial applicability with easier controlling of the reaction.

PROCESS FOR THE PREPARATION OF SILDENAFIL

The present invention is directed to a process for the preparation of the compound of Formula (I) : comprising the step of converting a compound selected from the group consisting of the compounds of formulae (II), (III) and (IV) : wherein X is halogen, in one or more steps to give the compound of formula (I). The invention is also directed to a process for the preparation of a pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. Moreover, the invention relates to intermediates suitable for use in the above processes as well as processes for their preparation.