Reference_01_08_2014_165529

The possibilities of synthesizing various α-trifluoromethylated oxygenated heterocycles, starting from trifluoroacetaldehyde Me hemiacetal, through classic cyclization reactions, have been demonstrated. In this way, sixmembered cyclic compds., δ-lactones and also macrolactone derivs., bearing a CF3 group in a position α to the oxygen could be easily obtained through a RCM reaction. Bicyclic compds. could be also synthesized by an intramol. PausonKhand reaction.

~6 Citings

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212. An efficient dehyrohalogenation method for the synthesis of α,β,β-trifluorostyrenes, α-chloro-β,β-difluorostyrenes and E-1-arylperfluoroalkenes

By Anilkumar, R.; Burton, Donald J.

From Journal of Fluorine Chemistry (2005), 126(8), 1174-1184. Language: English, Database: CAPLUS, DOI:10.1016/j.jfluchem.2005.05.005

Dehydrofluorination of 1-aryl-1,2,2,2-tetrafluoroethanes (ArCHFCF3) and 1-aryl-1-chloro-2,2,2-trifluoroethane (ArCHClCF3) using lithium hexamethyldisilazide (LHMDS) in THF at room temp. produced 1,2,2-trifluorostyrene and 1- chloro-2,2-difluorostyrene, resp., in very good isolated yields. Dehydrofluorination of 1,2,2,3,3,3-hexafluoro-1- phenylpropane (PhCHFCF2CF3) and 1,2,2,3,3,4,4,4-octafluoro-1-phenylbutane (PhCHFCF2CF2CF3) using LHMDS produced the corresponding substituted olefins (1-phenyl-1,2,3,3,3-pentafluoroprop-1-ene and 1-phenyl-1,2,3,3,4,4,4- pentafluorobut-1-ene) in good yield and high E-selectivity. Dehydrofluorination of 1-chloro-1-phenyl-2,2,3,3,3- pentafluoropropane (PhCHClCF2CF3) and 1-chloro-1-phenyl-2,2,3,3,4,4,4-heptafluorobutane (PhCHClCF2CF2CF3) produced a mixt. of the corresponding E and Z olefins (PhCCl=CFCF3 and PhCCl=CFCF2CF3) in good yield.

~12 Citings

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213. Preparation of isothiazole dioxides as CXCand CC-chemokine receptor ligands

By Taveras, Arthur G.; Zheng, Junying; Biju, Purakkattle J.; Yu, Younong; Chao, Jianhua; Fine, Jay; Lundell, Daniel; Priestley, Tony; Reggiani, Angelo; Merritt, J. Robert; et al

From PCT Int. Appl. (2005), WO 2005068460 A1 20050728, Language: English, Database: CAPLUS

Disclosed are novel compds. I [D, E = N, CR50; provided that D and E are not the same (one is N and the other is CR50); R50 = H, CF3, CN, etc.; A = (hetero)aryl, (hetero)arylalkyl; B = (hetero)aryl] and the pharmaceutically acceptable salts and solvates thereof. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenesis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and cardiac reperfusion injury, pain (e.g., acute pain, acute and chronic inflammatory pain, and neuropathic pain) using a compd. I. Although the methods of prepn. are not claimed, hundreds of example prepns. and/or characterization data are included. For example, II was prepd. in 68% yield from the isothiazoledioxide III and the amine IV.pTSA (prepn. of reactants given). Antagonist activities of some examples of I towards CXCR1, CXCR2 and CCR7 are given.

~7 Citings

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214. Preparation of five-membered heterocycle-substituted benzenepropanoic and related acids as selective S1P1 (EDG1) receptor agonists

By Colandrea, Vincent J.; Doherty, George A.; Hale, Jeffrey J.; Huo, Pei; Legiec, Irene E.; Toth, Leslie; Vachal, Petr; Yan, Lin

From PCT Int. Appl. (2005), WO 2005058848 A1 20050630, Language: English, Database: CAPLUS

The present invention encompasses five-membered heterocycle-substituted benzenepropanoic acids (shown as I; variables defined below; e.g. 3-[4-[5-(3-cyano-4-isopropyloxyphenyl)-1,2,4-oxadiazol-3-yl]-3-methylphenyl]propanoic acid (II)) as well as the pharmaceutically acceptable salts thereof. The compds. are selective S1P1/EDG1 receptor agonists and thus have immunosuppressive, antiinflammatory and hemostatic activities by modulating leukocyte trafficking, sequestering lymphocytes in secondary lymphoid tissues, and enhancing vascular integrity. The invention is also directed to pharmaceutical compns. contg. such compds. and methods of treatment or prevention. The example I have utility as immunoregulatory agents as demonstrated by their activity as potent and selective agonists of the S1P/Edg1 receptor over the S1P3/Edg3 receptor; in particular, the example I possess a selectivity for the S1P1/Edg1 receptor over the S1P3/Edg3 receptor of >100 fold as measured by the ratio of EC50 for the S1P1/Edg1 receptor to the EC50 for the S1P3/Edg3 receptor as evaluated in the 35S-GTPγS binding assay and possess an EC50 for binding to the S1P1/Edg1 receptor of <50 nM as evaluated by the 35S-GTPγS binding assay. Although the methods of prepn. are not claimed, >100 example prepns. are included. For example, II was prepd. in 2 steps by first cyclizing N-hydroxy-3-methyl-4-[2- (tert-butoxycarbonyl)ethyl]benzamidine with 3-cyano-4-isopropyloxybenzoic acid using N-(3-dimethylaminopropyl)-N'- ethylcarbodiimide in MeCN and then hydrolyzing the result. For I: R1, R2, R3 and R4 = H, F, Cl, Br, I, CN, OH, C1-6alkyl, C2-6alkenyl, C2-6alkynyl and C1-5alkoxy, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl and C1-5alkoxy are each (un)substituted with 1-3 F, Cl, Br, I, OH, C1-8alkoxy and -O2H, and any two of R1-R4 may be joined together with the atoms to which they are attached to form a satd. monocyclic ring of 3-8 atoms optionally contg. 1 or 2 O atoms. R5 = F, Cl, Br, I, CN, OH, or (un)substituted C1-4alkyl, C2-4alkenyl, C2-4alkynyl and C1-4alkoxy; R6 = (un)substituted Ph, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl and thienyl, and R6 may be substituted on two adjacent atoms to form a fused partially arom. (un)substituted bicyclic ring of 9-12 atoms optionally contg. one or two O or S groups, or both. U, V and W = - C(R9)- or -N-; X, Y and Z = -C(R11):, -O-, -N:, -N(R12)- and -S- such that the resulting ring together with Q and T form an arom. heterocycle; Q and T = >C: or >N-, with the proviso that both Q and T are not >N-; addnl. details are given in the claims.

~28 Citings

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215. Novel α-fluorinated cyclic phosphite and phosphinite ligands and their Rh-complexes as suitable catalysts in hydroformylation

By Odinets, Irina; Kegl, Tamas; Sharova, Elena; Artyushin, Oleg; Goryunov, Evgenii; Molchanova, Galina; Lyssenko, Konstantin; Mastryukova, Tatyana; Roeschenthaler, Gerd-Volker; Keglevich, Gyoergy; et al

From Journal of Organometallic Chemistry (2005), 690(14), 3456-3464. Language: English, Database: CAPLUS, DOI:10.1016/j.jorganchem.2005.04.038

Asym. cyclic phosphite and phosphinite ligands of a novel type bearing either a trifluoromethyl or pentafluorophenyl group were synthesized using >PCl or >PN< species and racemic fluorinated alcs. For example, 2,2,2-trifluoro-1-phenyl- 1-ethanol reacted with 2-chloro-1,3,2-benzodioxaphosphole giving 2-(2,2,2-trifluoro-1-phenylethoxy)-1,3,2- benzodioxaphospholene in 100% yield. The P-ligands were converted to complexes of RhIII(L)(Cp*)Cl2 type (where L = phosphite or phosphinite) and, in two instances, their stereostructures were evaluated by x-ray anal. These complexes along with in situ systems, formed from Rh(CO)2(acac) precursor and the corresponding ligand, were tested in the hydroformylation of styrene. Both systems provided excellent hydroformylation activities at 100 °C. Using the RhI in situ systems, moderate and high regioselectivities towards the branched aldehyde (2-phenylpropanal) were obtained at 100 and 40 °C, resp.

~7 Citings

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216. Preparation of substituted nicotinoylcarbamates as pesticides

By Ito, Masahito; Murata, Tetsuya; Araki, Koichi; Otsu, Yuichi; Shibuya, Katsuhiko; Nakakura, Norihiko From PCT Int. Appl. (2005), WO 2005047255 A1 20050526, Language: English, Database: CAPLUS

The title compds. I [m = 0-1; W = O, S; R2 = H, alkyl, aralkyl, etc.; R1 = (CR3R4)p(CHR5)qQ (wherein R3 = H, alkyl; R4 = H, alkyl, Ph, etc.; R5 = H, alkyl; p, q = 0-1; Q = (un)substituted aryl, 5-6 membered heterocyclyl that contains at least one hetero atom selected from N, O and S, etc.)], useful for controlling pests, were prepd. Thus, refluxing 4- trifluoromethylnicotinamide with oxalyl chloride in 1,2-dichloroethane benzyl alc. for 2 h followed by reacting the resulting intermediate with benzyl alc. afforded I [m = 0; W = O; R1 = CH2Ph; R2 = H] which showed 100% control of Myzus persicae (resistant to organophosphorous agents and carbamates) at 100 ppm.

~0 Citings

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217. Silicon-induced diastereoselectivity of the catalyzed phosphorylation of 1-(perfluoroalkyl)-ω-(trialkylsilyl)alkan-1-ols

By Molchanova, G. N.; Shcherbina, T. M.; Petrovskii, P. V.; Kudryavtsev, I. Yu.; Zakharov, L. S. From Russian Chemical Bulletin (2004), 53(9), 2013-2019. Language: English, Database: CAPLUS, DOI:10.1007/s11172-005-0064-3

The stereochem. of catalytic phosphorylation of 1-(perfluoroalkyl)-ω-(trialkylsilyl)alkan-1-ols with pentavalent phosphorus acid monochlorides (phosphonochloridates, methyl(phenyl)phosphinic chloride, and phosphorochloridates) was studied. The effects of the structures of alcs. and phosphorylating agents on the degree of the reaction diastereoselectivity were investigated. Methylphosphono chloridates were found to react most stereoselectively; the diastereoselectivity of the phosphorylation is independent of the donor or acceptor character of substituents at the phosphorus atom, being detd. by their vols. In the series of silylalkanols, the diastereoselectivity of the reaction the higher the closer the Si atom to the reactive site of the mol., the larger the vol. of the perfluoroalkyl substituent, and the more pronounced the electronwithdrawing properties of the substituents at the Si atom. A reaction mechanism is proposed that rationalizes the stereoselectivity of the reaction.

~0 Citings

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218. Preparation of pyrrolidinylquinolones as antibacterials

By Ellsworth, Edmund Lee; Sciotti, Richard John; Starr, Jeremy Tyson

From PCT Int. Appl. (2005), WO 2005026165 A1 20050324, Language: English, Database: CAPLUS

Title compds. [I; X = N, C; R1 = alkyl, haloalkyl, cycloalkyl, halocycloalkyl, aryl, heteroaryl; R2 = OH, OBF2, alkoxy, cycloalkyloxy, etc.; R3-R5 = halo, NH2, alkyl, haloalkyl, alkoxy, haloalkoxy; R1R5 = atoms to form a (substituted) 6- membered ring contg. an addnl. O, S, NH, NA1; A1 = alkyl; A = specified (substituted) (fused) 1-pyrrolidinyl], were prepd. Thus, title compd. (II) (prepn. outlined) showed min. inhibitory concns. of 0.008 μg/mL, 0.015 μg/mL, and 0.06 μg/mL against H. influenzae HI-3542, M. catarrhalis BC-3531, and E. coli EC-2549, resp.

~4 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

219. Preparation of alkoxybenzoylpiperazines as inhibitors of glycine transporter 1 (GlyT-1)

By Jolidon, Synese; Narquizian, Robert; Nettekoven, Matthias Heinrich; Norcross, Roger David; Pinard, Emmanuel; Stalder, Henri

From PCT Int. Appl. (2005), WO 2005014563 A1 20050217, Language: English, Database: CAPLUS

Title compds. I [wherein Ar = (un)substituted aryl or 6-membered heteroaryl; R1 = H, alkyl; R2 = H, alkyl, alkenyl, (un)substituted cycloalkyl, etc.; R3, R4, R6 = independently H, OH, halo, cyclo/alkyl, alkoxy; R5 = NO2, CN, CHO and derivs., SO2R10; R10 = (un)substituted alkyl; and their pharmaceutically acceptable acid addn. salts, with the exception of certain compds.] were prepd. as glycine transporter 1 (GlyT-1) inhibitors. For instance, reacting 2-isopropoxy-5- methylsulfonylbenzoic acid (prepn. given) with 1-(2-fluoro-4-trifluoromethylphenyl)piperazine gave piperazine II. I

showed an IC50 (μM) at GlyT-1 in the range of 0.006-5.0. Preferred I displayed an IC50 (μM) at GlyT-1 in the range of 0.006-0.05. Thus, I are useful in the treatment of illnesses based on the glycine uptake inhibitor, such as psychoses,

pain, neurodegenerative disfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.

~17 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

220. The first synthesis of chiral azulene alcohols possessing a trifluoromethyl group by lipase-mediated biotransformation

By Naoshima, Yoshinobu; Kimura, Takatomo; Mori, Yoshihiro; Kamezawa, Makoto; Tachibana, Hojun; Kohara, Kazuko; Ohtani, Takehiko

From Recent Research Developments in Organic & Bioorganic Chemistry (2004), 6, 1-9. Language: English, Database: CAPLUS

(R)-α-(Trifluoromethyl)-1-azulenemethanol derivs. I [R3-8 = H; R3 = Cl, Br, R4-8 = H; R3 = R8 = Me, R4 = R6 = H, R5 = CHMe2; R3 = R5 = H, R4 = R6 = R8 = Me] and their (S)-O-acylated derivs. II [R = COCH2Cl, CO(CH2)nMe, R3-8 = H, n = 0,

2] and II [R = COCH2Me; R3-8 = H; R3 = Cl, Br, R4-8 = H; R3 = R8 = Me, R4 = R6 = H, R5 = CHMe2; R3 = R5 = H, R4 = R6 = R8 = Me] were synthesized in enantiomerically pure form via lipase-catalyzed transesterification reactions of the

corresponding racemic alcs. (±)-I and vinyl esters, ROCH:CH2, using CHIRAZYINE L5 (Candida antarctica lipase type A, CALA). The abs. configuration of O-acylated derivs. and alcs. was assigned as S and R, resp., on the basis of stereoselectivity in lipase-mediated biotransformations, HPLC sepn. and elution order of enantiomers in columns.

~0 Citings

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221. The role of organic fluorine in directing alkylation reactions via lithium chelation

By Tenza, Kenny; Northen, Julian S.; O'Hagan, David; Slawin, Alexandra M. Z.

From Journal of Fluorine Chemistry (2004), 125(11), 1779-1790. Language: English, Database: CAPLUS, DOI:10.1016/j.jfluchem.2004.09.015

The fluorine of a fluoromethyl group displays a measurable chelation effect to lithium during α-methylation of an ester with lithium diisopropylamide (LDA) and Me iodide. A series of esters is compared with F, H and O, and the resultant diastereoselectivity is consistent with the intermediate capacity of F to chelate lithium relative to H and O. In a second system which involved comparing a tertiary org. fluorine with hydrogen, no such effect is apparent, most probably due to adverse steric effects. The abs. and relative stereochem. of the predominant diastereoisomers are confirmed by X-ray crystallog. of suitable cryst. derivs. in each case. It is concluded that there is a potential role for org.-bound fluorine to become involved in lithium chelation in well-designed enolate alkylation systems.

~5 Citings

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222. Remarkable Substituent Effects on the Oxidizing Ability of Triarylbismuth Dichlorides in Alcohol Oxidation

By Matano, Yoshihiro; Hisanaga, Teppei; Yamada, Hisatsugu; Kusakabe, Shingo; Nomura, Hazumi; Imahori, Hiroshi From Journal of Organic Chemistry (2004), 69(25), 8676-8680. Language: English, Database: CAPLUS, DOI:10.1021/jo0485740

Substituent effects on the oxidizing ability of triarylbismuth dichlorides were examd. by intermol. and intramol. competition expts. on geraniol oxidn. in the presence of DBU. The oxidizing ability of the dichlorides increases with increasing electron-withdrawing ability of the para substituents, and by introduction of a Me group at the ortho position of the aryl ligands attached to the Bi. The intermol. and intramol. H/D kinetic isotope effects obsd. for the competitive oxidn. of p- bromobenzyl alcs. indicate that the rate-detg. step involves C-H bond cleavage. Several primary and secondary alcs. were oxidized efficiently under mild conditions by the combined use of newly developed organobismuth(V) oxidants and DBU.

~8 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

223. Synthesis and Comparative Analysis of the Steric and Supramolecular Structures of Diastereomers of 4,4- Bis(trifluoromethyl)-2-(fluoroalkoxy)-6,7-benzo-1,3,2λ5- dioxaphosphepin-5-one 2-Oxides

By Gubaidullin, A. T.; Mironov, V. F.; Burnaeva, L. M.; Litvinov, I. A.; Dobrynin, A. B.; Goryunov, E. I.; Ivkova, G. A.; Konovalova, I. V.; Mastryukova, T. A.

From Russian Journal of General Chemistry (Translation of Zhurnal Obshchei Khimii) (2004), 74(6), 842-859. Language: English, Database: CAPLUS, DOI:10.1023/B:RUGC.0000042419.00823.95

Phosphorinane ring enlargement of 2-R1R2CHO-4H-1,3,2-benzodioxaphosphorin-4-ones ("salicylphosphites") by addn. of hexafluoroacetone gave benzodioxaphosphepins I (7-12; RF = CF3, R = Ph, 3-ClC6H4, 3-MeOC6H4, 3-CF3C6H4; RF = C3F7, R = Ph; RF = cyclo-C6F11, R = Me) as 1:1 diastereomeric mixts. Crystal structure of individual diastereomers crystd. from the diastereomeric mixts. are reported. The mol. and supramol. structure of the compds. were examd. in terms of the proposed model that takes account of the revealed effect of sepn. of hydrophilic and lipophilic regions in the crystal.

~4 Citings

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224. Preparation of 3,4-diaminocyclobutene-1,2-diones as CXC-chemokine receptor ligands

By Taveras, Arthur G.; Aki, Cynthia J.; Bond, Richard W.; Chao, Jianping; Dwyer, Michael; Ferreira, Johan A.; Chao, Jianhua; Yu, Younong; Baldwin, John J.; Kaiser, Bernd; et al

From U.S. Pat. Appl. Publ. (2004), US 20040147559 A1 20040729, Language: English, Database: CAPLUS

Title compds. [I; A = (substituted) pyridylmethyl, thiazolylmethyl, benzofurylmethyl, isoxazolylmethyl, pyrazinylmethyl, triazolylmethyl, phenylalkyl, etc.; B = (substituted) Ph, benzotriazolyl, benzimidazolyl, imidazolyl, pyrazolyl, hydroxypyridinyl, thienyl, pyrrolyl, isothiazolyl, etc.], were prepd. Thus, title compd. (II) (prepn. outlined) showed Ki = 0.8 nM in a CXCR2 SPA receptor binding assay.

~3 Citings

Copyright © 2014 American Chemical Society (ACS). All Rights Reserved.

225. Preparation of 3,4-di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands

By Taveras, Arthur G.; Aki, Cynthia J.; Bond, Richard W.; Chao, Jianping; Dwyer, Michael; Ferreira, Johan A.; Chao, Jianhua; Yu, Younong; Baldwin, John J.; Kaiser, Bernd; et al

From U.S. Pat. Appl. Publ. (2004), US 20040106794 A1 20040603, Language: English, Database: CAPLUS

Title compds. I [A = (un)substituted heterocycle, heterocyclylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, etc.; B = (un)substituted aryl, heteroaryl, heterocycle, heteroarylarene, etc.], or a pharmaceutically acceptable salt or solvate thereof, are prepd. and disclosed as cxc-chemokine receptor ligands. Thus, II was prepd. by substitution of (dimethylaminocarbonylhydroxyphenylamino)(ethoxy)cyclobutenedione [prepn. given] with (R)-2-amino-N,3- dimethylbutanamide monohydrochloride [prepn. given]. Compds. of the invention demonstrated an IC50 value of < 20 μM in CXCR1 SPA assay and < 5 μM in CXCR2 SPA assay. I are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.

~0 Citings

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226. Preparation of 3,4-di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands

By Taveras, Arthur G.; Aki, Cynthia J.; Bond, Richard W.; Chao, Jianping; Dwyer, Michael; Ferreira, Johan A.; Chao, Jianhua; Yu, Younong; Baldwin, John J.; Kaiser, Bernd; et al

From U.S. Pat. Appl. Publ. (2004), US 20040097547 A1 20040520, Language: English, Database: CAPLUS

Title compds. I [A = (un)substituted heterocycle, heterocyclealkyl, heteroaryl, heteroarylalkyl, cycloalkyl, etc.; B = (un)substituted aryl, heteroaryl, heterocycle, heteroarylarene, etc.], or a pharmaceutically acceptable salt or solvate thereof, are prepd. and disclosed as cxc-chemokine receptor ligands. Thus, II was prepd. by substitution of (dimethylaminocarbonylhydroxyphenylamino)(ethoxy)cyclobutenedione [prepn. given] with (R)-2-amino-N,3- dimethylbutanamide monohydrochloride [prepn. given]. Compds. of the invention demonstrated an IC50 value of < 20 μM in CXCR1 SPA assay and < 5 μM in CXCR2 SPA assay. I are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.