191212-74-5

Basic information

• Product Name: 4-(N-benzyl-N-methylamino)-1-[2-fluoro-3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine
• Synonyms: 4-(N-benzyl-N-methylamino)-1-[2-fluoro-3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine
• CAS NO: 191212-74-5
• Molecular Weight: 446.571
• Mol File: 191212-74-5.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: 4-(N-benzyl-N-methylamino)-1-[2-fluoro-3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(N-benzyl-N-methylamino)-1-[2-fluoro-3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine(191212-74-5)
• EPA Substance Registry System: 4-(N-benzyl-N-methylamino)-1-[2-fluoro-3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propyl]piperidine(191212-74-5)

Safety Data

• Hazardous Substances Data: 191212-74-5(Hazardous Substances Data)

Upstream product

• 124-63-0 methanesulfonyl chloride 
• 76167-62-9 4-(N-benzyl-N-methylamino)-piperidine 
• 10353-53-4 1,2-epoxy-5-hexene 
• 191351-60-7 methanesulfonic acid 2-fluoro-3-(5-[1,2,4]triazol-4-yl-1H-indol-3-yl)-propyl ester 
• 191212-85-8 (R,S)-2-fluoro-3-(5-(1,2,4-triazol-4-yl)-1H-indol-3-yl)propanol 
• 191212-83-6 tert-butyl(2-fluoro-hex-5-enyloxy)dimethylsilane 

Relevant articles and documents

PALLADIUM CATALYZED INDOLIZATION

We have found that 2-unsubstituted indoles of structural formula (IV) can be cost-effectively synthesized in high yield by the palladium-catalyzed coupling/ring closure of a 2-halo or 2-trifluoromethylsulfonyloxy aniline (I) and an acyl silane derivative (II), followed by deprotection of the silyl protecting groups. The process of the present invention is particularly useful to form indoles containing acid-labile substituents such as triazole, acetyl, ketal, cyano, and carbamate, or indoles having a good leaving group in the benzyl position. The advantages of the present process are that it does not require the use of triphenyl phosphine or tetrabutyl ammonium chloride or lithium chloride. When applied to 5-triazolyl substituted indoles, the present process also eliminates the tendency of triazolyl polymerization in the Fischer indole synthesis. Still further, the present invention is also directed to the novel intermediates of structural formulae (V) and (VI).

Fluorination of 3-(3-(piperidin-1-yl)propyl)indoles and 3-(3-(piperazin- 1-yl)propyl)indoles gives selective human 5-HT(1D) receptor ligands with improved pharmacokinetic profiles

It has previously been reported that a 3-(3-(piperazin-1- yl)propyl)indole series of 5-HT(1D) receptor ligands have pharmacokinetic advantages over the corresponding 3-(3-(piperidin-1-yl)propyl)indole series and that the reduced pK(a) of the piperazines compared to the piperidines may be one possible explanation for these differences. To investigate this proposal we have developed versatile synthetic strategies for the incorporation of fluorine into these ligands, producing novel series of 4- fluoropiperidines, 3-fluoro-4-aminopiperidines, and both piperazine and piperidine derivatives with one or two fluorines in the propyl linker. Ligands were identified which maintained high affinity and selectivity for the 5-HT(1D) receptor and showed agonist efficacy in vitro. The incorporation of fluorine was found to significantly reduce the pK(a) of the compounds, and this reduction of basicity was shown to have a dramatic, beneficial influence on oral absorption, although the effect on oral bioavailability could not always be accurately predicted.