- Acylation of 2-methoxypropene with anhydrides and halides of perfluorocarboxylic acids in the presence of tertiary amines
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3-Methoxy-1-(perfluoroalkyl)but-2-en-1-ones were synthesized by C-acylation of 2-methoxypropene with perfluorocarboxylic acid anhydrides, acid chlorides, and acid fluorides in the presence of tertiary amines.
- Gorlov,Kurykin,Petrova
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- Synthesis of new polyhalogenoalkyl-containing phosphonates with an enaminone core and their use in the preparation of fluorinated heterocycles
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A number of polyhalogenoalkyl-containing phosphonates with an enaminone core were synthesized from readily available β-alkoxyvinyl polyhalogenoalkyl ketones by successive bromination, amination, and Arbuzov reaction. The new phosphonates were used for the syntheses of five- and six-membered heterocycles bearing both trifluoromethyl and methylenephosphonate groups.
- Tarasenko, Karen V.,Manoylenko, Olga V.,Kukhar, Valery P.,R?schenthaler, Gerd-Volker,Gerus, Igor I.
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- Convergent synthesis and cytotoxicity of novel trifluoromethyl-substituted (1H-pyrazol-1-yl)(quinolin-4-yl) methanones
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A convergent synthesis of a series of 16 new polysubstituted (5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)(quinolin-4-yl)methanones, starting from isatin and alky(aryl/heteroaryl) ketones, is described. The diheteroaryl methanones were achieved at yields of up to 95% by a [3?+?2] cyclocondensation reaction involving 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluorobut-3-en-2-ones (by two-step reaction) and 2-alkyl(aryl/heteroaryl)-4-carbohydrazides (by three-step reaction). Subsequently, representative dehydrated heterocyclic derivatives were obtained from the respective 5-hydroxy-2-pyrazoline moieties by classical dehydration reactions, which resulted in the corresponding (5-(trifluoromethyl)-1H-pyrazol-1-yl)(quinolin-4-yl)methanones (three examples) at yields of 69–82%. The subsequent cytotoxicity evaluation showed that compounds with aromatic groups at the 2-position of the quinoline and a methyl moiety at the 3-position of the pyrazole have significant cytotoxicity in human leukocytes at high concentrations (200?μM).
- Bonacorso, Helio G.,Nogara, Pablo A.,Silva, Fernanda D'A.,Rosa, Wilian C.,Wiethan, Carson W.,Zanatta, Nilo,Martins, Marcos A.P.,Rocha, Jo?o B.T.
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- Identification of N-acyl 4-(3-pyridonyl)phenylalanine derivatives and their orally active prodrug esters as dual acting α4β1 and α4β7 receptor antagonists
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From a series of N-acyl 4-(3-pyridonyl)phenylalanine derivatives of 4, the trifluoromethyl derivative 28 was identified as a potent, dual acting alpha4 integrin antagonist with activity in primate models of allergic asthma. Investigation of a series of prodrug esters led to the discovery of the morpholinopropyl derivative 48 that demonstrated good intestinal fluid stability, solubility and permeability. Compound 48 gave high blood levels of 28 when dosed orally in cynomolgus monkeys. Surprisingly, hydrolysis of 48 was rapid in liver microsomes from the pharmacological species, mouse, rat and monkey, but slow in dog and human; in vivo studies also indicated there was prolonged exposure to unchanged prodrug in dogs.
- Tilley, Jefferson W.,Sidduri, Achyutharao,Lou, Jianping,Kaplan, Gerry,Tare, Nadine,Cavallo, Gary,Frank, Karl,Pamidimukkala, Anjula,Choi, Duk Soon,Gerber, Louise,Railkar, Aruna,Renzetti, Louis
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- Synthesis and [3,3]-sigmatropic rearrangements of 5-(pentafluorosulfanyl)-pent-3-en-2-ol, its homologues, and trifluoromethyl analogues
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The synthesis of aliphatic (pentafluoro-λ6-sulfanyl)(SF5)-substituted compounds is more challenging than that of the related CF3-substituted analogues. Previous investigations of [3,3]-sigmatropic rearrangements of γ-SF5-substituted allylic alcohols failed to yield 3-SF5-substituted carboxylic acid derivatives. Herein, we present the synthesis of a series of 1-SF5-alk-1-en-3-ols and our efforts to apply them in Johnson-Claisen, ester enolate-Claisen, and Ireland-Claisen rearrangements. Unfortunately, these reactions failed to include the 1-SF5-substituted 1,2-double bond, although successful reactions of analogous CF3-allylic alcohols were reported. Further experiments revealed that bulkiness rather than electronic properties of the SF5group prevented [3,3]-sigmatropic rearrangements. Indeed, the introduction of a competing second vinyl group into the system (1-SF5-penta-1,4-dien-3-ol) confirmed that a Johnson-Claisen rearrangement was successful (92% yield of methyl 7-SF5-hepta-4,6-dienoate) with incorporation of the unsubstituted 4,5-double bond while the 1-SF5-substituted 1,2-double bond remained unchanged. Efforts to apply 1-(SF5CF2)-substituted 1,2-double bond systems, which are similar to CF3analogues in steric requirements, in Johnson-Claisen or ester enolate-Claisen rearrangements failed because of the instability of the SF5CF2substituent under various reaction conditions. On the other hand, when the SF5group was separated from the reaction center by a CH2group instead (5-SF5-pent-3-en-2-ol), Johnson-Claisen rearrangements using six orthoesters provided the target 2-substituted 3-(CH2SF5)-hex-4-enoates in 55-76% yields as ～1?:?1 mixtures of diastereomers. As an example to demonstrate the utility of these products, methyl 3-(CH2SF5)-hex-4-enoate was reduced, and the formed alcohol was oxidized to the aldehyde. Finally, initial experiments showed that the synthetic sequence developed for SF5compounds is also applicable for analogous CF3-substituted allylic alcohols (5-CF3-pent-3-en-2-ol) and their Johnson-Claisen rearrangement.
- Haufe, Günter,Husstedt, Wibke S.,dudziński, piotr,matsnev, Andrej V.,thrasher, Joseph S.
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p. 5607 - 5623
(2021/07/02)
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- Influence of Trifluoromethyl Groups on the Crystal Packing of the Binuclear Copper(II) Complex Based on N2O3-Pentadentate (Hydroxy)bis(СF3-Enaminoketone)
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Abstract: The reaction of 1,1,1-trifluoro-4-methoxy-3-penten-2-one (L1) with 1,3-diaminopropan-2-ol affords N,N'-(2-hydroxypropane-1,3-diyl)bis(trifluoroacetylacetimine) (H3L2) in a yield of 82%. In the absence of additional bases, the synthesized N2O3 ligand reacts with copper(II) acetate to give the binuclear complex [Cu2L2(OAc)] (I), the structure of which is determined by X-ray structure analysis (CIF file CCDC no. 2071133).
- Edilova, Yu. O.,Kudyakova, Yu. S.,Slepukhin,Burgart, Ya. V.,Saloutin,Bazhin
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p. 631 - 637
(2021/09/15)
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- 3-Substituted pyrazoles and 4-substituted triazoles as inhibitors of human 15-lipoxygenase-1
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Investigation of 1N-substituted pyrazole-3-carboxanilides as 15-lipoxygenase-1 (15-LOX-1) inhibitors demonstrated that the 1N-substituent was not essential for activity or selectivity. Additional halogen substituents on the pyrazole ring, however, increased activity. Further development led to triazole-4-carboxanilides and 2-(3-pyrazolyl) benzoxazoles, which are potent and selective 15-LOX-1 inhibitors.
- Pelcman, Benjamin,Sanin, Andrei,Nilsson, Peter,No, Kiyo,Schaal, Wesley,?hrman, Sara,Krog-Jensen, Christian,Forsell, Pontus,Hallberg, Anders,Larhed, Mats,Boesen, Thomas,Kromann, Hasse,Vogensen, Stine Byskov,Groth, Thomas,Claesson, Hans-Erik
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p. 3024 - 3029
(2015/06/22)
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- 6-Hydrazinonicotinic acid hydrazide: A useful precursor for chemo- and regioselective synthesis of new heteroaryl-linked pyridinohydrazones
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In order to demonstrate the reactivity differentiation between the two dinucleophilic centers in the 6-hydrazinonicotinic acid hydrazide hydrate (1), a series of seven new 6-[(2-(arylidene)hydrazinyl]nicotinohydrazides (4) was chemoselectively accessed from the reaction of 1 with seven aryl or heteroaryl aldehydes by a simple procedure in ethanol as solvent. In a subsequent study, cyclization reactions of 4 with some 4-alkoxy-1, 1, 1-trifluoroalk-3-en-2-ones or triethylorthoacetate were proceeded easily also in ethanol, an eco-friendly solvent, to give regioselectively nine examples of pyrazolinyl- pyridinohydrazones and one 1, 3, 4-oxadiazole derivative, respectively, as stable and pure compounds in good yields. ARKAT-USA, Inc.
- Bonacorso, Helio G.,Paim, Gisele R.,Porte, Liliane M.F.,Pittaluga, Everton P.,Martins, Marcos A.P.,Zanatta, Nilo
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p. 214 - 225
(2012/10/29)
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- Regioselective sy nthesis and antimicrobial evaluation of new 1-aryloxyacetyl-, 1-thiophenoxyacetyl- and 1-phenylaminoacetylsubstituted 3-alkyl(aryl/heteroaryl)-5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles
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This paper describes an efficient approach for the regioselective synthesis of new series of twenty 1-aryloxy(thio)acetyl and 1-(phenylamino)acetyl- substituted 5-trifluoromethyl-5-hydroxy-4,5-dihydro-1H-pyrazoles (3) in 34-96% yields from the cyclocondensation reaction of 4-alkoxy-4-alkyl-(aryl/heteroaryl) -1,1,1-trifluoroalk-3-en-2-ones with different substituted acetohydrazides. Dehydration reactions of 3, carried out in the presence of thionyl chloride, furnished two examples of aromatic 5-trifluoromethyl-1H-pyrazole derivatives, in 78-82% yields. From antimicrobial tests the fungi C. albicans proved to be particularly susceptible to the action of 1-(phenylamino)acetyl-substituted 3-alkyl-2-pyrazoline derivatives; however the first results are still weak when compared to standard drugs. ARKAT-USA, Inc.
- Bonacorso, Helio G.,Pittaluga, Everton P.,Alves, Sydney H.,Schaffer, Larissa F.,Cavinatto, Susiane,Porte, Liliane M. F.,Paim, Gisele R.,Martins, Marcos A. P.,Zanatta, Nilo
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experimental part
p. 62 - 75
(2012/07/31)
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- The first application of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones in a three-component condensation protocol for the synthesis of 3-acyl-4-aryl-2- (trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-ones
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The one-pot, simple and efficient three-component condensation protocol for the preparation of a series of twenty-five new 3-acyl-4-aryl-2- (trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-ones, where aryl = Ph, 4-tolyl, 4-ClPh, 4-NO2
- Bonacorso, Helio G.,Navarini, Jussara,Wiethan, Carson W.,Bortolotto, Guilherme P.,Paim, Gisele R.,Cavinatto, Susiane,Martins, Marcos A.P.,Zanatta, Nilo,Caro, Miguel S.B.
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body text
p. 160 - 165
(2011/05/02)
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- Convergent procedure for the synthesis of trifluoromethyl-containing N-(pyridinyl-triazolyl)pyrimidin-2-amines
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This study describes a simple and efficient procedure to synthesize a novel series of fourteen 4-substituted N-(5-pyridinyl-1H-1,2,4-triazol-3-yl)-6- (trifluoromethyl)pyrimidin-2-amines, where the 4-substituents are H, CH 3, C6H
- Bonacorso, Helio G.,Bortolotto, Guilherme P.,Navarini, Jussara,Porte, Liliane M.F.,Wiethan, Carson W.,Zanatta, Nilo,Martins, Marcos A.P.,Flores, Alex F.C.
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scheme or table
p. 1297 - 1301
(2011/02/22)
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- PYRAZOLES USEFUL IN THE TREATMENT OF INFLAMMATION
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There is provided compounds of formula (I), wherein R1, R2, X1, X2 and n have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a lipoxygenase (e.g. 15-lipoxygenase) is desired and/or required, and particularly in the treatment of inflammation.
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Page/Page column 56
(2008/06/13)
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- PYRAZOLE COMPOUNDS USEFUL IN THE TREATMENT OF INFLAMMATION
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There is provided compounds of formula (I), wherein R1, R2, Ra and Rb have meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful in the treatment of diseases in which inhibition of the activity of a lipoxygenase (e.g. 15-lipoxygenase) is desired and/or required, and particularly in the treatment of inflammation.
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Page/Page column 42-43
(2010/10/20)
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- O-N, S-N AND N-N EXCHANGE REACTIONS AT OLEFINIC CARBON ATOMS: FACILE SYNTHETIC METHOD FOR β-TRIFLUOROACETYLVINYLAMINES
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β-Trifluoroacetylvinyl ethers 1 and sulfides 2 react easily with various amines at room temperature to give β-trifluoroacetylvinylamines 3 in excellent yields.This O-N and S-N exchange reaction can be extended to N-N exchange reaction.
- Hojo, Masaru,Masuda, Ryoichi,Okada, Etsuji,Sakaguchi, Syuhei,Narumiya, Hitoshi,Morimoto, Katsushi
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p. 6173 - 6176
(2007/10/02)
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- A Useful One-Step Synthesis of β-Trihaloacetylvinyl Ethers and Trihaloacetylketene Acetals
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Trifluoro- and trichloroacetylation of ethyl orthoacetate and some methyl ketone acetals affords the corresponding acylketene acetals and α-substituted β-acylvinyl ethers, respectively, in high yields.
- Hojo, Masaru,Masuda, Ryoichi,Okada, Etsuji
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p. 1013 - 1014
(2007/10/02)
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