- N-vinylation and N-allylation of 3,5-disubstituted pyrazoles by N-H insertion of vinylcarbenoids
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A vinylcarbenoid approach toward N-functionalization of NH-pyrazoles is presented. The rhodium(II)- catalyzed reaction of methyl styryl-diazoacetate (1) or dimethyl 2-diazoglutaconate (3) with 3,5-disubstituted pyrazoles gave products of carbenoid N-H insertion in high combined yields, although regioselectivity issues posed by the pyrazole or the vinylcarbenoid moiety as well as positional and configurational isomerism concerning the C,C double bond of the latter led to product mixtures. The ambident reactivity of the vinylcarbenoid derived from 1 could be steered by the catalyst: While Rh2(OAc)4 yielded products of direct carbenoid insertion preferentially, silver(I) catalysis strongly favored reaction at the vinylogous site of the carbenoid resulting in an N-allylation of the pyrazoles.
- Gill, Agagia,Werz, Udo R.,Maas, Gerhard
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- Design, synthesis, biological evaluation and in silico studies of pyrazole‐based nh2‐acyl oseltamivir analogues as potent neuraminidase inhibitors
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Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti‐influenza therapy. The 150‐cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150‐cavity
- Ye, Jiqing,Lin, Lin,Xu, Jinyi,Chan, Paul Kay-Sheung,Yang, Xiao,Ma, Cong
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- Intramolecular Cyclization of Vinyldiazoacetates as a Versatile Route to Substituted Pyrazoles
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Vinyldiazo compounds undergo a thermal electrocyclization to form pyrazoles in yields of up to 95percent. The reactions are operationally simple, use readily available starting materials, require no intervention of a catalyst, and enable the synthesis of mono-, di- A nd tri-substituted pyrazoles. With the ability to produce highly substituted pyrazoles and the flexibility in installing various types of substituents, this method constitutes a new entry to this valuable heterocyclic scaffold and may be of interest to all branches of the chemical industry.
- Drikermann, Denis,G?rls, Helmar,Kerndl, Valerie,Vilotijevic, Ivan
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p. 1158 - 1162
(2020/07/20)
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- New Zinc Catalyst for Hydrosilylation of Carbonyl Compounds
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A new zinc complex was synthesized and applied in the catalytic hydrosilylation of carbonyl compounds. Optimization of the reaction conditions showed that the presence a substoichiometric amount of methanol accelerates the process significantly. The reaction can proceed at very low catalyst load (down to 0.1 molpercent) under mild reaction conditions. The reaction tolerates the presence of C=C bonds, and thus can be useful for the synthesis of allylic alcohols from α,β-unsaturated aldehydes and ketones.
- Alshakova, Iryna D.,Nikonov, Georgii I.
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p. 3305 - 3312
(2019/08/28)
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- FUSED TRICYCLIC PYRAZOLO-DIHYDROPYRAZINYL-PYRIDONE COMPOUNDS AS ANTIVIRALS
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The invention provides compounds of Formula (I) as described herein, along with pharmaceutically acceptable salts, pharmaceutical compositions and pharmaceutical combinations containing such compounds, as well as methods to use these compounds, salts and compositions for treating viral infections, particularly infections caused by hepatitis B virus (HBV), and for reducing the occurrence of serious conditions associated with HBV.
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- The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor
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The process development and kilogram-scale synthesis of beclabuvir (BMS-791325, 1) is described. The convergent synthesis features the use of asymmetric catalysis to generate a chiral cyclopropane fragment and coupling with an indole fragment via an alkyl
- Bien, Jeffrey,Davulcu, Akin,Delmonte, Albert J.,Fraunhoffer, Kenneth J.,Gao, Zhinong,Hang, Chao,Hsiao, Yi,Hu, Wenhao,Katipally, Kishta,Littke, Adam,Pedro, Aghogho,Qiu, Yuping,Sandoval, Maria,Schild, Richard,Soltani, Michelle,Tedesco, Anthony,Vanyo, Dale,Vemishetti, Purushotham,Waltermire, Robert E.
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p. 1393 - 1408
(2018/09/06)
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- Thermally induced N-S bond insertion reaction of diazo compounds with: N -sulfenylsuccinimides: Synthesis of sulfides and mechanism studies
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A metal-free gem-functionalization reaction of diazo compounds with N-sulfenylsuccinimides via a formal N-S bond insertion process has been reported. The transformation features mild reaction conditions, broad substrate scope and functional group tolerance, offering an efficient approach to sulfide synthesis in moderate to high yields. In addition, the mechanism studies indicate the formation of free carbene under thermal conditions followed by ylide generation, then N-S bond cleavage and C-N bond formation occurred in sequence to give the sulfide products.
- Zhang, Xiaolu,Zheng, Yang,Qiu, Lihua,Xu, Xinfang
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supporting information
p. 70 - 76
(2017/12/27)
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- Synthesis of Nitrogen Heterocycles via Photochemical Ring Opening of Pyridazine N-Oxides
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A photochemical method for the direct synthesis of 1H-pyrazoles from pyridazine N-oxides was developed. This chemistry features a regioselective approach to nonsymmetrically substituted pyridazine N-oxides. Herein, we highlight the first strategic use of photoinduced ring-opening reactions of 1,2-diazine N-oxides for the preparative synthesis of nitrogen heterocycles.
- Portillo, Maribel,Maxwell, Michael A.,Frederich, James H.
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p. 5142 - 5145
(2016/10/14)
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- Development of a simple system for the oxidation of electron-rich diazo compounds to ketones
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Mild heating of diazo compounds in DMSO furnishes ketone products in moderate to excellent yields. The reaction is particularly effective on electron-rich substrates and exhibits high chemoselectivity, allowing for the use of diazo compounds containing additional oxidation-prone functional groups. This straightforward protocol offers an alternate route to synthetically useful α-ketoesters from readily available aryl diazoacetates.
- O'Connor, Nicholas R.,Bolgar, Peter,Stoltz, Brian M.
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supporting information
p. 849 - 851
(2016/02/05)
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- When aryldiazonium salts meet vinyl diazoacetates: A cobalt-catalyzed regiospecific synthesis of N-arylpyrazoles
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A cobalt-catalyzed C-N bond formation between aryl diazonium salts and vinyl diazoacetates has been developed under relatively mild conditions. The N-arylpyrazoles have been prepared in moderate to high yields in a regiospecific way.
- Guo, Haiheng,Zhang, Daming,Zhu, Chenghao,Li, Jian,Xu, Guangyang,Sun, Jiangtao
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supporting information
p. 3110 - 3113
(2014/06/23)
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- PAR2 RECEPTOR ANTAGONISTS
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Compounds of formula (I) or pharmaceutically acceptable salts, solvates or hydrates thereof wherein P, Q, X, Y, R1, R2, R3, R10, R11, and R12 are as defined in the claims, and the use those compounds in medicine.
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Page/Page column 51
(2014/02/16)
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- RECEPTOR ANTAGONISTS
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N-(4-carbamimidoylphenyl)-amide derivatives having utility in therapy as PAR2 receptor antagonists.
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Page/Page column 36
(2014/02/16)
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- Rh(iii)-catalyzed C-H activation/[4 + 3] cycloaddition of benzamides and vinylcarbenoids: Facile synthesis of azepinones
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Vinylcarbenoids are used as three-carbon components in Rh(iii)-catalyzed C-H activation/[4 + 3] cycloaddition with benzamides to access azepinones. This transformation makes a feature of simple starting materials, mild reaction conditions and high efficiency. A kinetic isotope effect study was conducted and a plausible mechanism is proposed.
- Cui, Sunliang,Zhang, Yan,Wang, Dahai,Wu, Qifan
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p. 3912 - 3916
(2013/09/23)
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- Synthesis and anticancer activity of heteroaromatic linked 4β-amido podophyllotoxins as apoptotic inducing agents
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A series of different heteroaromatic linked 4β-amidopodophyllotoxin conjugates (16a-i, 17a-i and 18a-d) were synthesized and evaluated for anticancer activity against five human cancer cell lines. Among the series, one of the compound 17g showed significant antiproliferative activity in A549 (lung cancer) cell line. Flow cytometric analysis showed that 17g arrested the cell cycle in the G2/M phase leading to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and DNA fragmentation assay also suggests that 17g induces cell death by apoptosis.
- Kamal, Ahmed,Tamboli, Jaki R.,Vishnuvardhan,Adil,Nayak, V. Lakshma,Ramakrishna
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p. 273 - 280
(2013/02/25)
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- NOVEL COMPOUNDS
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This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.
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Paragraph 0547; 0548
(2013/06/26)
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- PYRAZOLE KINASE MODULATORS AND METHODS OF USE
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The present invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferationm, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/0r modulate kinases. Methods of using the compounds and pharmaceutical compositions thereof to treat kinase-dependent diseases and conditions are also an aspect of the invention.
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Page/Page column 77
(2010/10/20)
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- Inhibitors of acyl-coA:cholesterol O-acyltransferase. 2. Identification and structure-activity relationships of a novel series of N-alkyl-N- (heteroaryl-substituted benzyl)-N'-arylureas
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A series of N-alkyl-N-(heteroaryl-substituted benzyl)-N'-arylurea and related derivatives represented by 2 and 3 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Among these novel compounds, the type 3 series was superior. A pyrazol-3-yl group on the N-benzyl group of this trisubstituted urea (i.e. 3, Ar1 = pyrazol-3- yl) was identified as a heteroaromatic ring providing a good profile of biological activity. As a result of optimization of the combination with the N-alkyl group (R) and N-aryl group (At3), compound 3aq (FR186054) was identified as a new, orally efficacious ACAT inhibitor, which exhibited potent in vitro ACAT inhibitory activity (rabbit intestinal microsomes IC50 = 99 nM) and excellent hypocholesterolemic effects in cholesterol-fed rats, irrespective of administration mode (ED50 = 0.046 mg/kg dosed via the diet, ED50 = 0.44 mg/kg administered by gavage in PEG400 vehicle). Moreover, a toxicological study revealed compound 3aq to be nontoxic to the adrenal glands of dogs when tested at a single dose of 10 mg/kg po.
- Tanaka, Akira,Terasawa, Takeshi,Hagihara, Hiroyuki,Sakuma, Yuri,Ishibe, Noriko,Sawada, Masae,Takasugi, Hisashi,Tanaka, Hirokazu
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p. 2390 - 2410
(2007/10/03)
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- Synthesis of Aryl- and Hetarylpyrazoles
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Hetaryldieneamines (1) react with sulfonyl azides to give 3-hetarylpyrazoles (5).Similarly, N,N-dimethyl-4-phenyldieneamine-2-carboxylic acid methyl ester (6) affords 3-phenylpyrazole-5-carboxylic acid methyl ester (7). - Keywords: Cycloaddition; Dieneami
- Timari, G.,Hajos, Gy.,Messmer, A.,Gelleri, A.
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p. 1037 - 1040
(2007/10/02)
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- Azolides, 7. - Phosphonate and Phosphate Group Transfer with Pyrazolides
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The tert-butylammonium α-diazophosphinates 7 add onto acceptor-substituted acetylenes 8 with formation of N-phosphorylpyrazoles: Primarily formed 3H-pyrazoles 9 undergo spontaneous sigmatropic shift of the anionic PO-group to yield 10. α-Diazophosph
- Regitz, Manfred,Martin, Roland
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p. 1641 - 1652
(2007/10/02)
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