2-Trifluoromethyl-3- piperazine

With respect to a new C-substituent, only 2-(trifluoromethyl)piperazine was synthesized and studied by JH NMR spectroscopy (95RTC97). The six-membered ring exists in the chair conformation and the CF3 group occupies exclusively the equatorial position. 

Chemical Name 4-[3- [2-(trifluoromethyl)-9H-thioxanthen-9-ylidenel propyl] -1-piperazine-ethanol... 

The sodium derivative of the 2-trifluoromethylphenothiazine was prepared from 26.7 g (0.1 mol) of 2-trifluoromethylphenothiazine and 2.3 g (0.1 g atom) of sodium in 500 ml of liquid ammonia. After the reaction was completed, the ammonia was driven off and 500 ml of dry toluene were added. A solution of 25 g (0.09 mol) of N-(3-chloropropyl)-N -[2-(1,3-dioxanyl)-ethyl] -piperazine In 200 ml of toluene was added drop by drop to this solution which was then refluxed with stirring for 1B hours. After cooling, the precipitate which had formed was filtered and the filtrate was washed with water, dried and concentrated in vacuo. 33 g of brown oil, the N-3-(2-trifluoromethyl-10-phenothiazinyl)-propyl-N -2-[2-(1,3-dioxanyl)] -ethyl-piperazine, were obtained. 

The crystal structures of 4-phenyl-2- 4-[4-(2-pyrimidinyl)piperazin-l-yl]butyl -2,3,5,6,7,8-hexahydro-177-pyrido[l,2-c][l,3]oxazine-l,3-dione <1995ZK899>, 4-cyano-l-phenyl-l-trifluoromethyl-2,3-dihydro-l/7-pyrido[l,2-r-]pyrimidin-... 

Hutzler, J.M., Steenwyk, R.C., Smith, E.B., Walker, G.S. and Wienkers, L.C. (2004) Mechanism-based inactivation of cytochrome P450 2D6 by l-[(2-ethyl-4-methyl-1 H-imidazol-5-yl) methyl]-4-[4-(trifluoromethyl)-2-pyridinyl]piperazine kinetic characterization and evidence for apoprotein adduction. Chemical Research in Toxicology, 17 (2), 174—184. 

Ordinarily, alkyl nitrate esters will not nitrate amines under neutral conditions. However, Schmitt, Bedford and Bottaro have reported the use of some novel electron-deficient nitrate esters for the direct At-nitration of secondary amines. The most useful of these is 2-(trifluoromethyl)-2-propyl nitrate, which nitrates a range of aliphatic secondary amines to the corresponding nitramines in good to excellent yields. Nitrosamine formation is insignificant in these reactions. 2-(Trifluoromethyl)-2-propyl nitrate cannot be used for the nitration of primary amines, or secondary amines containing ethylenediamine functionality like that in piperazine. Its use is limited with highly hindered amines or amines of diminished nucleophilicity due to inductive or steric effects. 

Treatment of 18 with ethylenediamine afforded the desired triazolo piperazine 3 at room temperature albeit in low yields. Attempts to improve the reaction revealed that when the oxadiazole was added to two equivalents of ethylenediamine in methanol at 0 °C, a new species crystallized directly from the reaction mixture. This solid was isolated, identified as the amidine 20, and was found to convert to 3 by refiuxing in methanol for 4h (Scheme 5.11). The formation of amidine 20 was curious since it suggested that initial attack of ethylenediamine did not occur at the carbon of the oxadiazole vicinal to the trifluoromethyl group. Of the three carbons of the oxadiazole which need to react with ethylenediamine, this would easily be rationalized as the most electrophilic. In order to understand the mecha-... 

Chemical Name N-3-(2-Trifluoromethyl-10-phenothiazinyl)-propyl-N -2-[2-(l,3-dioxanyl)]ethyl-piperazine disuccinate... 

In the presence of a strong base, trifluoromethylacetophenone trifluoromethylates thioxanthone a haloform reaction is involved <2003TL1055>. l-(Af-benzylpiperazino)-2,2,2-trifluoroethanol and iV-trifluoroacctyl-iV-benzyl-piperazine behave in a similar manner (Scheme 88) <2001EJ01467, 2003SL230>. 

Ethyl l-cyclopropyl-4-oxo-7-phenylsulfonyl-6-trifluoromethyl-l,4-dihydro-l,8-naphthyridine-3-carboxylate (7) gave the crude ester (8, R = Et) (piperazine, MeCN, 20°C), characterized after saponification to l-cyclopropyl-4-oxo-7-(piperazin-l-yl)-6-trifluoromethyl-l,4-dihydro-1,8-naphthyri dine-3-car-boxylic acid (8, R = H) (NaOH, EtOH 37% overall).1167... 

Trifluoromethyl-2 -deoxyuridine (C10H11F3N2O5) 5-Trifluoromethyluracil (C5H3F3N2O2) l-(3-Trifluoromethylphenyl)piperazine (C11H13F3N2)... 

Two syntheses of triazolopiperazines 80 and 89 are shown in Schemes 12.11 and 12.12. The piperazine ring of 80 can be constmcted by either intramolecular condensation-cyclization of ethylene diamine with chloroacetyl moiety (Scheme 12.11) or hydrogenation of the corresponding triazolopyrazine 87 and 88 (Scheme 12.12). The 3-trifluoromethyl[l,2,4]triazolering of 80 was constructed by intramolecular dehydration of 83. The overall yield of 80 via oxodiazole 82 is satisfactory, however, yields of 3-pentafluoroethyl and 2,2,2-trifluoroethyl 89 via 2-hydrazopyrazine are affected by low yield of 88 (Scheme 12.12). 

Fluphenazine (2-[4-[3-[2-(Trifluoromethyl)-10H-phenothiazin-10-yl]-propyl]piperazin-l-yl]ethanol, Prolixin)... 

FLuphenazine Hydrochloride is 4- 3-1 2-(trifluoromethyl)-phenothiazine-lO-yl] propyl piperazine ethanol dihydrochloride also 4-(3-[10 -2(-trifluoromethyl)-phenothiazinyl ] propyl)- -piperazine-ethanol dihydrochloride 1-(2-hydroxy ethyl)-4- [2-trifluoromethyl-lO-phenothiazinyl) propyl ] piperazine dihydrochloride 10-(3 - [4 -... 

Bevan S, Winter J (1995) Nerve growth factor (NGF) differentially regulates the chemosensitivity of adult rat cultured sensory neurons, J Neurosci 15 4918 926 Bhattacharya A, Scott BP, Nasser N, et al, (2007) Pharmacology and antitussive efficacy of 4-(3-trifluoromethyl-pyridin-2-yl)-piperazine-l-carboxylic acid (5-trifluoromethyl-pyridin-2-yl)-amide (JNJ17203212), a transient receptor potential vanilloid 1 antagonist in guinea pigs, J Pharmacol Exp Ther 323 665-674... 

The approach to 3-trifluoromethyl-tetrahydro-l,2,4-triazaolo-/4,3-a/-pyrazine (3-trifluoromethyl-l,2,4-triazaolo-piperazine), the heterocyclic portion of the sitagliptin molecule, requires construction of the annulated ring on 2-chloropyrazine 4 to yield the intermediate 7. The latter is selectively hydrogenated in step iv to 8, maintaining the five-membered heteroaromatic ring. 

Py pyrrole, MPy 1-methylpyrrole, PPy polypyrrole, PMPy poly(l-methylpyrrole), EDOT 3,4-ethylenedioxytiophene, PEDOT poly(3,4-ethylenedioxytiophene), MT 3-methylthiophene, PMT poly(3-methylthiopliene), NaPSS sodium polystyrene sulfonate, NaDBS sodium dodecylbenzenesulfonate, NaPTS sodium para-toluene sulfonate, BSA benzenesulfonic acid, SSA 2-hydroxy-5-sulfobenzoic acid, MES 2-(Af-morpholino) ethanesulfonic acid, MOPS 3-(Al-morpholino) propanesulfonic acid, PIPES piperazine-l,4-bis(2-ethanesulfonic) acid, MeCN acetonitrile, DCE 1,2-dichloroetane, BU4NPF6 tetrabutylammonium hexafluor-ophosphate, BTPPA-CIO4 bis(triphenylphosphoranylidene)ammonium perchlorate, BTPPA-TFPB bis(triphenylphosphoranylidene)ammonium tetrakis[3,5-bis (trifluoromethyl)phenyl]borate, TPenA tetraphenylammonium... 

Li, Wang, and others described piperazine-thiourea (198)-catalyzed Michael-hemiketalization of a-cyanoketones 197 to a,P-unsaturated trifluoromethyl ketones 196a [78a] or trichloromethyl ketones [78b] 196b, which provided access to a-trifluoromethyl-or trichloromethyl-dihydropyrans with good stereoselectivities (Scheme 2.53). 

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