306293-41-4

Basic information

• Product Name: (2,4-dimethyl-1-oxidopyridin-3-yl){4-methyl-4-[(3S)-3-methyl-4-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}piperazin-1-yl]piperidin-1-yl}methanone
• Synonyms: methanone, (2,4-dimethyl-1-oxido-3-pyridinyl)[4-methyl-4-[(3S)-3-methyl-4-[(1S)-1-[4-(trifluoromethyl)phenyl]ethyl]-1-piperazinyl]-1-piperidinyl]-; Piperidine, 1-((2,4-dimethyl-1-oxido-3-pyridinyl)carbonyl)-4-methyl-4-((3S)-3-methyl-4-((1S)-1-(4-(trifluoromethyl)phenyl)ethyl)-1-piperazinyl)-; Piperidine, 1-[(2,4-dimethyl-1-oxido-3-pyridinyl)carbonyl]-4-methyl-4-[(3S)-3-methyl-4-[(1S)-1-[4-(trifluoromethyl)phenyl]ethyl]-1-piperazinyl]-
• CAS NO: 306293-41-4
• Molecular Formula: C₂₈H₃₇F₃N₄O₂
• Molecular Weight: 518.6142
• Mol File: 306293-41-4.mol

Chemical Properties

• Boiling Point: 644.1°C at 760 mmHg
• Flash Point: 343.3°C
• Density: 1.23g/cm³
• Vapor Pressure: 1.76E-16mmHg at 25°C
• Refractive Index: 1.571
• CAS DataBase Reference: (2,4-dimethyl-1-oxidopyridin-3-yl){4-methyl-4-[(3S)-3-methyl-4-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}piperazin-1-yl]piperidin-1-yl}methanone(CAS DataBase Reference)
• NIST Chemistry Reference: (2,4-dimethyl-1-oxidopyridin-3-yl){4-methyl-4-[(3S)-3-methyl-4-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}piperazin-1-yl]piperidin-1-yl}methanone(306293-41-4)
• EPA Substance Registry System: (2,4-dimethyl-1-oxidopyridin-3-yl){4-methyl-4-[(3S)-3-methyl-4-{(1S)-1-[4-(trifluoromethyl)phenyl]ethyl}piperazin-1-yl]piperidin-1-yl}methanone(306293-41-4)

Safety Data

• Hazardous Substances Data: 306293-41-4(Hazardous Substances Data)

Upstream product

• 372156-99-5 3-carboxy-2,4-dimethylpyridine 1-oxide 
• 544704-12-3 2-methyl-4-(4-methylpiperidin-4-yl)-1-[1-(4-trifluoromethylphenyl)ethyl]piperazine 
• 1737-26-4 1-(4-trifluorophenyl)ethanol 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 1737-26-4 (R)-1-[4-(trifluoromethyl)phenyl]ethan-1-ol 
• 306297-00-7 tert-butyl 4-methyl-4-((S)-3-methyl-4-((S)-1-(4-(trifluoromethyl)phenyl)ethyl)piperazin-1-yl)piperidine-1-carboxylate 
• 306296-99-1 4-Cyano-4-{(S)-3-methyl-4-[(S)-1-(4-trifluoromethyl-phenyl)-ethyl]-piperazin-1-yl}-piperidine-1-carboxylic acid tert-butyl ester 
• 306296-87-7 1-[4(trifluoromethyl)-α(S)-methylbenzyl]-2(S)-methyl-4-(tert-butoxycarbonyl)piperazine 
• 306296-89-9 (S)-2-Methyl-1-[(S)-1-(4-trifluoromethyl-phenyl)-ethyl]-piperazine 
• 306296-86-6 [(1R)-1-[4-(trifluoromethyl)phenyl]ethyl] methanesulfonate 
• 147081-29-6 (S)-3-methyl-piperazine-1-carboxylic acid tert-butyl ester 
• 74879-18-8 (S)-2-methylpiperazine 
• 872850-48-1 tert-butyl 4-isocyanato-4-methylpiperidine-1-carboxylate 
• 828935-40-6 tert-butyl 4-(2-(((S)-1-methoxy-1-oxopropan-2-yl)((S)-1-(4-trifluoromethylphenyl)ethyl)amino)-2-oxoethylamino)-4-methyl-piperidine-1-carboxylate 

Relevant articles and documents

Forward- and reverse-synthesis of piperazinopiperidine amide analogs: A general access to structurally diverse 4-piperazinopiperidine-based CCR5 antagonists

Piperazinopiperidine amide analogs are among the most promising CCR5 antagonists. As an effective extension of a previously-reported methodology to synthesize such compounds, forward- and reverse-syntheses were successfully developed in which the convergent synthesis of the piperazinopiperidine nucleus, with a building block of 4-substituent-4-aminopiperidine, served as a common key step. The two-way approach affords a comprehensive access to the piperazinopiperidine templated library with variation on the pharmacophore sites. Thus, a SAR study of our synthesized piperazinopiperidine-based CCR5 antagonists was conducted with respect to the structure and configuration of the substituent on the piperazine ring. The S-configuration of the benzylic-substituent is vital for the CCR5 binding, and the bulky or aryl substituent on the 2-position in the piperazine ring is detrimental to the activity. By using the forward-synthesis approach, the best compound in the chiral piperazine-based CCR5 antagonist series, Sch-D (Vicriviroc), was conveniently synthesized in an excellent yield. The Royal Society of Chemistry.

An improved synthesis of piperazino-piperidine based CCR5 antagonists with flexible variation on pharmacophore sites

An improved and efficient synthetic route towards piperidino-piperazine based CCR5 antagonists was developed. The new approach was flexible for introducing various substituents in the pharmacophore sites via Grignard reagent addition and reductive amination. l-Amino acids were used as a chiral pool to introduce and then induce the desired stereochemistries, meanwhile rendering the variable substitution. The efficient construction of the piperazino-piperidine nucleus was achieved in a highly convergent manner with a key building block of N1-Boc-4-substituent-4-aminopiperidine, exhibiting significant advantages in terms of concise synthetic route and environmental-friendly reagents over the previously described stepwise synthesis, in which a modified Strecker reaction was involved with highly toxic reagents such as diethylaluminum cyanide.

Facile synthesis of 4-substituted-4-aminopiperidine derivatives, the key building block of piperazine-based CCR5 antagonists

4-Substituted-4-aminopiperidine is an interesting structural motif found in a number of bioactive compounds. An efficient and convenient method for the synthesis of 4-differently substituted-4-aminopiperidine derivatives was described, employing isonipecotate as a starting material and Curtius rearrangement as a key step. The alkylation of isonipecotate could introduce various substituents at the 4-position of the piperidine ring. With this key building block, we are able to efficiently synthesize piperazino-piperidine based CCR5 antagonist in a highly convergent manner free of using toxic reagents such as diethylaluminum cyanide. The concise synthesis of a potent bioavailable CCR5 antagonist as HIV-1 entry inhibitor, Sch-350634 (1) was accomplished in excellent yield using N′-Boc-4-methyl-4-aminopiperidine 5a as a smart building block. The new methodology provides a facile and practical access to the piperazino-piperidine amide analogs as HIV-1 entry inhibitors.

Piperazine derivatives useful as CCR5 antagonists

The use of CCR5 antagonists of the formula or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, pyridyl, thiophenyl or naphthyl; R1is hydrogen or alkyl; R2is substituted phenyl, substituted heter

Piperazine-based CCR5 antagonists as HIV-1 inhibitors. II. Discovery of 1-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4methyl-4-[3(S)-methyl-4-[1(S)-[4- (trifluoromethyl) phenyl]ethyl]-1-piperazinyl]piperidine N1-oxide (Sch-350634), an orally bioavailable, poten

Truncation of the original piperidino-2(S)-methyl piperazine lead structure 2, from a family of muscarinic antagonists, gave compound 8 which has improved selectivity for the HIV-1 co-receptor CCR5 over muscarinic receptors. Further optimization for pharm