A new synthesis of 4-amino-2-quinolinones

Bergman, Jan; Brynolf, Anna; Vuorinen, Eino

doi:10.1016/s0040-4020(01)87337-3

Cited by 18 publications

(11 citation statements)

References 18 publications

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“…This should be disfavoured because of the low electrophilicity of the carbonyl functionality, but in the case where X = Cl, this was nevertheless the preferred outcome of the reaction. A similar precedent has previously been reported 9 by Párkányi, who found that methyl N-chloroacetylanthranilate cyclized to N-chloromethyl-4-quinazolinone ( 9) when treated with ammonia, while methyl N-bromoacetylanthranilate gave 1,4-benzodiazepin-2,5-dione (10) under the same reaction conditions (Scheme 2). In order to favour the formation of the desired benzodiazepine 1 we used the bromo-substituted starting material 4.…”

Section: Resultssupporting

confidence: 82%

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Synthesis of 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones by addition of Grignard reagents to derivatives of o-aminobenzonitrile

2009

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Addition of organometallics to N-(alpha-haloacyl)-o-aminobenzonitrile resulted in the formation of 2,5-disubstituted 1,4-benzodiazepin-3-ones, whereas N-(beta-haloacyl)-o-aminobenzonitrile gave 2,6-disubstituted 1,5-benzodiazocin-4-ones under similar conditions. Initial cylization of N-(beta-haloacyl)-o-aminobenzonitrile to obtain the corresponding lactam (e.g.alpha,alpha-dimethyl-N-(2-cyanophenyl)-beta-lactam) increased the yield of 1,5-benzodiazocin-4-ones significantly. Somewhat surprisingly, addition of lithium reagents to N-(beta-haloacyl)-o-aminobenzonitrile gave 4,4-disubstituted quinazolines via Grob fragmentation.

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Section: Resultssupporting

confidence: 82%

“…Addition of alkyl Grignard reagents and lithium regents (BuLi, PhLi) to 4 failed to give benzodiazepines, and instead 4-amino-2-quinolinones were formed, via halogen-metal exchange at the a-carbon as previously reported by Bergman et al 10 Addition of LiCl or TMEDA did not change the outcome of this reaction.…”

Section: Methodssupporting

confidence: 69%

Synthesis of 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones by addition of Grignard reagents to derivatives of o-aminobenzonitrile

2009

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“…Only a small number of 4-amino-3-alkyl/aryl-1H-quinolin-2-ones 5 have been described so far. They were prepared starting from 4-hydroxy-2-quinolones, 10-12 4-halogeno-2-quinolones, 11, 13-14 2-aminobenzenecarbonitriles, [15][16][17][18][19] and 2-bromobenzonitrile. 20 Compounds 5 have been employed in the synthesis of indolo[3,2-c]quinolin-6-ones and dibenzonaphtyridine-6,11-diones.…”

Section: Discussionmentioning

confidence: 99%

Thermal reaction of 3aH,5H-thiazolo[5,4-c]quinoline-2,4-diones – an easy pathway to 4-amino-1H-quinolin-2-ones and novel 6H-thiazolo[3,4-c]quinazoline-3,5-diones

Mrkvička¹,

Klásek²,

Kimmel³

et al. 2008

Arkivoc

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S-(3-Alkyl/aryl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)thiocarbamates 3 were thermally reacted to form 4-hydroxy-1H-quinolin-2-ones 1. Under the same reaction conditions, 3a-alkyl/aryl-[1,3]thiazolo[5,4-c]quinoline-2,4(3aH,5H)-diones 4 reacted to yield one of two different types of products, depending on the nature of substituent at the 5 position. Substitution with an alkyl or aryl group produced 4-amino-3-alkyl/aryl-1H-quinolin-2-ones 5, whereas the N-5 unsubstituted analogues rearranged to form novel 6H-thiazolo[3,4-c]quinazoline-3,5-diones 6 in high yields. The reaction mechanisms for the above transformations are discussed. All new products were characterized by NMR, MS and IR spectra. The structure of 1-butyl-9-methyl-6H-thiazolo[3,4-c]quinazoline-3,5-dione 6b was confirmed by single-crystal X-ray diffraction analysis.

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“…A solution of 2-bromo-2-methylpropanoylbromide was added to a well-stirred 2-phase system composed of K 2 CO 3 in water and 30 in CH 2 Cl 2 to give (Z)-2-bromo-N-(2-cyanovinyl)-2-methylpropanamide (31). Treatment of 31 with a solution of ethylmagnesium bromide under reflux conditions followed by quenching in a mixture of ice and aqueous NH 4 Cl provided 3,3-dimethylpyridine-2,4(1H,3H)-dione (32) [12] . Hydrogenation of the double bond followed by coupling of 33 with aryllithium gave the final product 4-(4chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-2-one (34) which was isolated after reversed phase chromatographic purification.…”

Section: Synthesis Of Chlorophenyl [ 14 C]-mln3897 (18)mentioning

confidence: 99%

“…The homoallylic bromide was susbsequently acylated with [1-14 C]-acetyl chloride under Friedel-Crafts conditions to provide (E)-1-[5-(3-bromopropylidene)-5,11-dihydro-10-oxa-1-aza dibenzo[a,d]cyclohepten-7-yl]-[1-14 C]ethanone (10) in 80% yield. Grignard addition of methyl magnesium bromide completed the synthesis of 11, which was subsequently alkylated with the chiral piperidinol (12). The desired product 13 was isolated by flash chromatographic purification.…”

mentioning

confidence: 99%

10th international symposium on the synthesis and applications of isotopes and isotopically labelled compounds—applications of isotopes in pharmacology, clinical and medical research Session 16, Wednesday, June 17, 2009

Elmore

Maxwell

2010

Labelled Comp Radiopharmac

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Diverse topics, with a central theme are discussed. On the one hand, the preparation of an anti-epidermal growth factor MAB, labelled with 177 Lu is detailed. In addition, traditional syntheses of isotopically labelled small molecules are also highlighted. Lu-anti-EGF-Mab using a macrocyclic ligand, DOTAM (2,2 0 ,2 00 ,2 000 -(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetamide) and its in vivo biodistribution in animal models. DOTAM-EGF was synthesized in high yield at room temperature in 0.1 M NaHCO 3 pH 8.2 using a mixture of DOTAM/anti-EGF-Mab in nonstoichiometric ratio. The complex was then labeled with 177 Lu (15 mCi 177 LuCl 3 , pH 4) with more than 95% labeling efficiency. Biodistribution evaluation revealed a major accumulation in periferal tumor tissues (up to 12.49% ID/g) at 24 h after i.v. injection while the tumor mass uptaked 7 times less activity. The liver, kidneys, and small intestine showed a moderate took up, the mean value was 3.4 ID/g in the first two hours post injection following a decreasing curve up to 0.5% ID/g at 72 h post injection. Based of the preliminary results of this study 177 Lu-(DOTAM)anti-EGF-Mab will be tested as a new radiopharmaceutical for epidermal malignancies.Keywords: epidermal growth factor; lutetium-177; targeted radiotherapy Introduction: One of the latest approaches in cancer therapy implies the use of a high linear energy transfer, nonpenetrating radiation specifically delivered at cellular level. Receptor-mediated radiotherapy (also called targeted radiotherapy, TRT) relies on the use of a receptor specific ligand to transport a radionuclide to tumor cells that overexpress the target receptor. The selection of the ligand is based on its ability to selectively target cancer cells. The therapeutic radiation is delivered to tumors while minimizing radiation exposure to normal tissues. In this concept, the radioligand should be rapidly cleared from circulation; the chelate should be stable under physiological conditions; the tumor cells should express a sufficiently high density of receptors and a long biological residence time of radioactivity is needed. The receptor internalization is the basic process that sustains the selectivity and therapeutic efficacy of targeted radiotherapy while the radioactive metabolites should remain trapped in the cell. Researchers are investigating both the agents that seek out specific tumor cells for treatment and the radioisotope payload that delivers the radiation.The EGFR (Epidermal Growth Factor Receptor) is a validated anticancer target. The physiological roles of EGFR ensure epidermal renewal and integrity. Alterations in the EGFR family are involved in the development of cancer leading to the stimulation of tumor growth, protection from apoptosis, angiogenesis, and the formation of metastases

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A new synthesis of 4-amino-2-quinolinones

Cited by 18 publications

References 18 publications

Synthesis of 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones by addition of Grignard reagents to derivatives of o-aminobenzonitrile

Synthesis of 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones by addition of Grignard reagents to derivatives of o-aminobenzonitrile

Thermal reaction of 3aH,5H-thiazolo[5,4-c]quinoline-2,4-diones – an easy pathway to 4-amino-1H-quinolin-2-ones and novel 6H-thiazolo[3,4-c]quinazoline-3,5-diones

10th international symposium on the synthesis and applications of isotopes and isotopically labelled compounds—applications of isotopes in pharmacology, clinical and medical research Session 16, Wednesday, June 17, 2009

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