194602-23-8

Usage

Uses

Used in Pharmaceutical Industry:
2-ETHOXY-5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]BENZOIC ACID is used as a reactant in the synthesis of Sildenafil Citrate (S435000), an orally active selective type 5 cGMP phosphodiesterase inhibitor. 2-ETHOXY-5-[(4-METHYLPIPERAZIN-1-YL)SULFONYL]BENZOIC ACID plays a crucial role in the development of treatments for erectile dysfunction and other related conditions by enhancing blood flow to the genital area.

Upstream product

• 109-01-3 1-methyl-piperazine 
• 200575-16-2 2-ethoxy-5-chlorosulphonyl-benzoic acid 
• 530-62-1 1,1'-carbonyldiimidazole 
• 134-11-2 2-ethoxybenzoic acid 
• 383427-86-9 2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)benzonitrile 
• 60638-81-5 5-chlorosulfonyl-2-hydroxy-benzoicacid methylester 
• 119-36-8 methyl salicylate 
• 215299-33-5 2-ethoxy-5-(4-methyl-1-piperazinesulphonyl)benzoic acid hydrochloric acid triethylamine 

Downstream Products

• 1370409-67-8 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 
• 139755-92-3 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 
• 1370409-68-9 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-1-methyl-3-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 
• 1370409-62-3 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-3-phenyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 
• 1370409-65-6 5-(2-ethoxy-5-((4-methylpiperazin-1-yl)sulfonyl)phenyl)-3-propyl-1-(pyridin-3-yl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one 
• 139755-83-2 viagra 

Relevant academic research and scientific papers

Preparation method of sildenafil citrate

The invention discloses a preparation method of sildenafil. The method comprises the following steps: activating an intermediate compound B in an aprotic solvent by using thionyl chloride, reducing with 1-methyl-4-nitro-3-propyl-1H-pyrazole-5-formamide in a zinc powder-ammonium chloride system in the presence of an acid-binding agent to obtain an intermediate compound E, and condensing to obtain an intermediate compound C; and cyclizing the intermediate compound C in an alcohol solvent under an alkaline condition to prepare sildenafil. The preparation method disclosed by the invention is short in reaction time, greatly shortens the production period so as to reduce the production cost, and is simple in operation and suitable for large-scale production.

Efficient and Practical Synthesis of Sulfonamides Utilizing SO2 Gas Generated on Demand

A simple and practical protocol was developed for the synthesis of sulfonamides by reacting organometallic reagents with SO2 gas generated on demand. SO2 was generated from readily available reagents safely in a highly contained and controlled fashion. The protocol allows the synthesis of sulfonamides without using either atom-inefficient SO2 surrogates or a SO2 cylinder that requires stringent storage regulations in the laboratory. The protocol was successfully applied to the synthesis of sildenafil.

Organic synthesis in a modular robotic system driven by a chemical programming language

The synthesis of complex organic compounds is largely a manual process that is often incompletely documented. To address these shortcomings, we developed an abstraction that maps commonly reported methodological instructions into discrete steps amenable to automation. These unit operations were implemented in a modular robotic platform by using a chemical programming language that formalizes and controls the assembly of the molecules. We validated the concept by directing the automated system to synthesize three pharmaceutical compounds, diphenhydramine hydrochloride, rufinamide, and sildenafil, without any human intervention. Yields and purities of products and intermediates were comparable to or better than those achieved manually. The syntheses are captured as digital code that can be published, versioned, and transferred flexibly between platforms with no modification, thereby greatly enhancing reproducibility and reliable access to complex molecules.

2-PHENYL-3,4-DIHYDROPYRROLO[2,1 -F] [1,2,4]TRIAZINONE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS AND USES THEREOF

The present invention relates to compounds of formula (I) or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein R1 is C1-C3alkyl optionally substituted with F, C3-C6cycloalkyl, C1-C3alkoxy; X represents a bond or C1-C3alkylene optionally substituted with OH, ONO, ONO2; R2 is H, OH, ONO, ONO2, C(O)OH, C(O)OC1-C3alkyl, CHO, CN, C1-C3alkoxy, OC(O)H, OC(O)-C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(0)N(R6)OR7, S(O0-2)C1-C3alkyl, CR8=N-OR9, CR8=N-NR10R11, CR8=NR12 or CR8=N-ONO2; R3 is C1-C6alkyl optionally substituted with F, OH, ONO, ONO2, C1-C3alkoxy, C3-C6cycloalkyl; C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkynyl; R4 is C1-C6alkyl optionally substituted with C3-C6cycloalkyl, C1-C6alkoxy, F, ONO, ONO2; C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl; R5 is H, SO2NR13R14, NHSO2NR13R14; R6 is H or C1-C3alkyl; R7 is H, C1-C3alkyl, C1-C3alkoxy, C1-C3alkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C1-C3alkyl, F; R8 is H, CH3 or C2H5; R9: H, C1-C3alkyl optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3alkyl, C1-C3alkoxy, OC(O)H, OC(O)-C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl; R10 and R11 are each independently H, C1-C3alkyl optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3, C1-C3alkoxy, OC(O)H, OC(O)-C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl;i or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is optionally substituted with C1-C3 alkyl; R12 is C1-C3 alkyl optionally substituted with OH, ONO, ONO2, CN, COOH, COOC1-C3alkyl, C1-C3alkoxy, OC(O)H, OC(O)-C1-C3alkyl, C(O)N(R6)OR7, OC1-C3alkylene-C(O)OH, OC1-C3alkylene-C(O)OC1-C3alkyl, OC1-C3alkylene-C(O)N(R6)OR7, S(O0-2)C1-C3alkyl; R13 and R14 are each independently H or C1-C6alkyl optionally substituted with F, OH, ONO, ONO2, COOH, C1-C3alkoxy, C3-C6Cycloalkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine, homopiperazine, 2,5-diazabicyclo[2,2,1]heptane and 3,7-diazabicyclo[3,3,0]octane, wherein said heterocyclic ring is optionally substituted with R15; R15 is C1-C6alkyl optionally substituted with halogen, OH, ONO, ONO2, C1-C3alkoxy, C1-C3haloalkoxy, COOR16, NR17R18, C=NR19, or with a tetrazole group which is optionally substituted with C1-C3alkyl; or a heteroaryl ring which is optionally substituted with F, wherein the at least one heteroatom of said heteroaryl ring is nitrogen; R16 is H, or C1-C4alkyl optionally substituted with F, OH, ONO, ONO2, NR17R18, or with a heteroaryl ring, wherein the at least one heteroatom of said heteroaryl ring is nitrogen, and wherein preferably said heteroaryl ring is selected from pyrrolidine, piperidine, piperazine, morpholine, pyrrole, and imidazole, wherein nitrogen atom is directly bound to C1-C4 alkyl; R17 and R18 are each independently H or C1-C4alkyl optionally substituted with ONO, ONO2; R19 is C1-C4alkyl optionally substituted with F, ONO, ONO2; C3-C6Cycloalkyl; and their use in methods of treating or preventing a disease alleviated by inhibition of PDE-5 in a human or in a non-human mammal.

Method for preparing 2-ethyoxyl-5-(4-methyl piperazine-1-sulfonyl) benzoic acid from methyl salicylate

The invention relates to a method for preparing 2-ethyoxyl-5-(methyl piperazine-1-sulfonyl) benzoic acid from methyl salicylate. The method comprises the following steps: taking the methyl salicylate as a raw material, sulfonating with chlorosulfonic acid

Pyrazolopyrimidinones which inhibit type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP PDE5) for the treatment of sexual dysfunction

Compounds of formulae (IA) and (IB) or pharmaceutically or veterinarily acceptable salts thereof, or pharmaceutically or veterinarily acceptable solvates of either entity, wherein R1 is C1 to C3 alkyl substituted with C3 to C6 cycloalkyl, CONR5R6 or a N-linked heterocyclic group; (CH2)nHet or (CH2)nAr; R2 is C1 to C6 alkyl; R3 is C1 to C6 alkyl optionally substituted with C1 to C4 alkoxy; R4 is SO2NR7R8; R5 and R6 are each independently selected from H and C1 to C4 alkyl optionally substituted with C1 to C4 alkoxy, or, together with the nitrogen atom to which they are attached, form a 5- or 6-membered heterocyclic group; R7 and R8, together with the nitrogen atom to which they are attached, form a 4-R10-piperazinyl group; R10 is H or C1 to C4 alkyl optionally substituted with OH, C1 to C4 alkoxy or CONH2; H is an optionally substituted C-linked 5- or 6-membered heterocyclic group; Ar is optionally substituted phenyl; and n is 0 or 1; are potent and selective cGMP PDE5 inhibitors useful in the treatment of, inter alia, male erectile dysfunction and female sexual dysfunction.

The chemical development of the commercial route to sildenafil: A case history

This paper is a case history of the chemical development of sildenafil which covers various aspects of work in chemical development namely: route selection, scale-up issues, the development of an efficient synthesis with high throughput, process safety, and environmental issues. Interesting chemical points include improved methods of preparing pyrazolo[4,3-d]-pyrimidines and the unusual isolation of an intermediate as its double salt (10). The potential dangers of nitrating pyrazole-5-carboxylic acids which are activated to a decarboxylation reaction are discussed.

Process for preparing sildenafil

A process for the preparation of a compound of formula (I): STR1 which comprises cyclization of a compound of formula (II): STR2