- Regioselective Radical Arene Amination for the Concise Synthesis ofortho-Phenylenediamines
-
The formation of arene C-N bonds directly from C-H bonds is of great importance and there has been rapid recent development of methods for achieving this through radical mechanisms, often involving reactiveN-centered radicals. A major challenge associated with these advances is that of regiocontrol, with mixtures of regioisomeric products obtained in most protocols, limiting broader utility. We have designed a system that utilizes attractive noncovalent interactions between an anionic substrate and an incoming radical cation in order to guide the latter to the areneorthoposition. The anionic substrate takes the form of a sulfamate-protected aniline and telescoped cleavage of the sulfamate group after amination leads directly toortho-phenylenediamines, key building blocks for a range of medicinally relevant diazoles. Our method can deliver both free amines and monoalkyl amines allowing access to unsymmetrical, selectively monoalkylated benzimidazoles and benzotriazoles. As well as providing concise access to valuableortho-phenylenediamines, this work demonstrates the potential for utilizing noncovalent interactions to control positional selectivity in radical reactions.
- Gillespie, James E.,Morrill, Charlotte,Phipps, Robert J.
-
supporting information
p. 9355 - 9360
(2021/07/19)
-
- Method for methylation reaction
-
The invention relates to a method for a methylation reaction. The method is characterized in that a reaction substrate is reacted in an organic solvent in the presence of an alkali with methyl trifluoroacetate as a methylation reagent to obtain a corresponding methylated product. The method is a new methylation method, and has the advantages of cheapness, easiness in operation, mild reaction conditions, wide application range of the substrate, avoiding of dimethyl sulfate, iodomethane and other highly toxic methylation reagents, and obtaining of the methylated product with a high yield.
- -
-
Paragraph 0013
(2019/01/21)
-
- Unexpected synthesis of azepino[4,3,2-cd]indoles from 4-aminoindoles
-
Unexpected regioselectivity for the Skraup-Doebner-Von Miller reaction was observed during the synthesis of quinolines from 4-aminoindoles and acetone in the presence of hydrochloric acid as a catalyst. The products were unambiguously assigned as 1-alkyl-
- Halaiev, Olexandr,Garazd, Myroslav,Gzella, Andrzej,Lesyk, Roman
-
supporting information
p. 1324 - 1325
(2017/03/10)
-
- Lewis acid-catalyzed electrophilic trifluoromethylthiolation of (Hetero)arenes
-
(N-Trifluoromethylthio)saccharin has been applied as an electrophilic trifluoromethylthiolating reagent for a broad scope of heteroarenes, electron-donating group (EDG)-activated benzenes, and several electron-rich olefins. Iron(III) and gold(III) catalysts showed complementary activity for different substrates.
- Wang, Qiang,Qi, Zisong,Xie, Fang,Li, Xingwei
-
supporting information
p. 355 - 360
(2015/03/05)
-
- 7H-PYRROLO[2,3-H]QUINAZOLINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESIS
-
A 7H-pyrrolo[2,3-h]quinazoline compound of the formula I wherein Ar, R1, R2, R7, R8, R9, R10, R11, R12, and n are as defined in the specification, and methods for maki
- -
-
Page/Page column 21
(2009/09/25)
-
- Synthesis and in vitro and in vivo antitumor activity of 2-phenylpyrroloquinolin-4-ones
-
In our search for potential new anticancer drugs, we designed and synthesized a series of tricyclic compounds containing the antimitotic 2-phenylazaflavone chromophore fused to a pyrrole ring in a pyrroloquinoline structure. Compounds 8, 18, 19, 22, 23, 25 and 26, when tested against a panel of fourteen human tumor cell lines, showed poor in vitro cytotoxic activity, whereas 20, 21 and 24 showed significant activity (IC50 0.7 to 50 μM). Steroid hormone-sensitive ovary, liver, breast and adrenal gland adenocarcinoma cell lines displayed the highest sensitivity (IC50 0.7 to 8 μM). Compound 24 blocked cells in the G2/M phase of the cell cycle and induced a significant increase in apoptotis. Compounds 20, 21 and 24 proved to alter microtubule assembly and stability, displaying a cytoplasmic microtubule network similar to that caused by Vincristine. In vivo, administration of compound 24 to Balb/c mice inhibited the growth of a syngenic hepatocellular carcinoma.
- Ferlin, Maria Grazia,Chiarelotto, Gianfranco,Gasparotto, Venusia,Dalla Via, Lisa,Pezzi, Vincenzo,Barzon, Luisa,Palu, Giorgio,Castagliuolo, Ignazio
-
p. 3417 - 3427
(2007/10/03)
-
- Discovery of a New Class of Anilinoquinazoline Inhibitors with High Affinity and Specificity for the Tyrosine Kinase Domain of c-Src
-
Deregulated activity of the nonreceptor tyrosine kinase c-Src is believed to result in signal transduction, cytoskeletal and adhesion changes, ultimately promoting a tumor-invasive phenotype. We report here the discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of the c-Src enzyme. Special attention was directed toward finding inhibitors selective against KDR tyrosine kinase in order to ensure that the in vivo profile of a specific Src inhibitor could be determined. The 4-aminobenzodioxole quinazoline series gave compounds with excellent potency and selectivity. The most interesting compounds were evaluated in vivo and displayed good pharmacokinetics following oral dosing. Compounds such as the aminobenzodioxoles were shown to be potent inhibitors of tumor growth in a c-Src-transformed 3T3 xenograft model in vivo, resulting in more than 90% growth inhibition at doses as low as 6 mg/kg po once daily. Src tyrosine kinase inhibitors such as these may provide a novel therapeutic modality for targeting cancer invasion and metastasis.
- Plé, Patrick A.,Green, Tim P.,Hennequin, Laurent F.,Curwen, Jon,Fennell, Michael,Allen, Jack,Lambert-Van Der Brempt, Christine,Costello, Gerard
-
p. 871 - 887
(2007/10/03)
-
- Cell proliferation inhibitors
-
Compounds having formula (I) inhibit cellular proliferation. Processes for the preparation of the compounds, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds are disclosed.
- -
-
-
- A practical method for N-methylation of indoles using dimethyl carbonate
-
A new method for N-methylation of indoles using environmentally safe and less toxic methylating reagent, dimethyl carbonate (DMC), has been developed. The effect of various functional groups on the indole ring has been investigated. This method provides the desired product in high yields with high purity and is suitable for large-scale production. This process was used successfully in a 300-gal reactor train for N-methylation of 6-nitroindole.
- Jiang, Xinglong,Tiwari, Ashish,Thompson, Maethonia,Chen, Zhihong,Cleary, Thomas P.,Lee, Thomas B. K.
-
p. 604 - 608
(2013/09/07)
-
- Methylation of indole compounds using dimethyl carbonate
-
A process for manufacturing a methylated indole compounds of the formula: where R1is selected from the group consisting of halogen, C1-C6alkyl, C1-C6alkenyl, —OCH3, —NO2, —CHO, —CO2CH3, and —CN, and R2is selected from the group consisting of C1-C6alkyl, —CO2CH3, —CN, —CHO, —NH2, —N(C1-C6alkyl)2, —(CH2)nCOOH, and —(CH2)nCN, where n is an integer from 1 to 4, inclusive, involves reacting a compound of the formula: with dimethyl carbonate in the presence of a base or a catalyst at ambient pressure.
- -
-
-
- Inhibitors of Protein Kinase C. 1. 2,3-Bisarylmaleimides
-
The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described.These 2,3-bisarylmaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a.Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11 μM).In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67 μM).Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).
- Davis, Peter D.,Hill, Christopher H.,Lawton, Geoffrey,Nixon, John S.,Wilkinson, Sandra E.,et al.
-
p. 177 - 184
(2007/10/02)
-
- Alkylation with Oxalic Esters. Scope and Mechanism.
-
Alkyl oxalates are well suited for use as standard synthetic reagents in N-, O-, or S-alkylations and often display an interesting regioselectivity.The mechanism seems to be a direct alkylation of the substrate anion.
- Bergman, Jan,Norrby, Per-Ola,Sand, Peter
-
p. 6113 - 6124
(2007/10/02)
-
- Synthesis of Indoles via Ring Closure of 2-Alkylnitroaniline Derivatives.
-
A variety of nitroindoles have been prepared from imidate, amidine, and sec-anilide derivatives of 2-alkyl-3- or 5-nitroanilines by a base-induced cyclization promoted by dialkyl oxalates.It is shown that essentially the same procedure also can be used to synthesize the corresponding nitroindole-3-glyoxylates in one simple operation.The synthetic potential is discussed and a mechanism is proposed.
- Bergman, Jan,Sand, Peter
-
p. 6085 - 6112
(2007/10/02)
-
- A NEW SIMPLE PROCEDURE FOR ALKYLATION OF NITROGEN HETEROCYCLES USING DIALKYL OXALATES AND ALKOXIDES.
-
A variety of nitrogen heterocycles are N-alkylated in high yields with dialkyl oxalates and potassium alkoxides in refluxing dimethylformamide.
- Bergman, Jan,Sand, Peter
-
p. 1957 - 1960
(2007/10/02)
-