1769-84-2Relevant academic research and scientific papers
Development of concise two-step catalytic approach towards lasofoxifene precursor nafoxidine
Johansson Seechurn, Carin C.C.,Gazi? Smilovi?, Ivana,Colacot, Thomas,Zanotti-Gerosa, Antonio,?asar, Zdenko
, p. 2691 - 2697 (2018)
We have elaborated a two-step catalytic approach to nafoxidine, a key precursor to lasofoxifene. Firstly, an efficient α-arylation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one with chlorobenzene was developed, which operates at low 0.1 mol% Pd-132 catalyst loading in the presence of 1.9 equivalents of sodium tert-butoxide at 60 °C in 1,4-dioxane and provides 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one in 90% yield. Secondly, we have demonstrated that 6-methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one can be converted to nafoxidine in 61% yield via CeCl3 promoted reaction with (4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)lithium, which is formed in-situ from the corresponding arylbromide precursor and n-butyllithium. Altogether, the shortest two-step approach to nafoxidine from simple tetralone commodity starting material has been developed with overall 55% yield. The developed synthetic approach to nafoxidine has several beneficial aspects over the one used in the synthetic route primarily developed for the preparation of lasofoxifene.
ESTROGEN RECEPTOR TARGETING ANTAGONISTS
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Paragraph 0024; 0088-0090, (2020/05/07)
The present disclosure relates to compounds that act as antagonists via binding to the ER ligand binding domain non-covalently or covalently, or act as both antagonists and ER protein degraders, and the synthesis of the same. Further, the present disclosure teaches the utilization of such compounds in a treatment for proliferative diseases, including cancer, particularly breast cancer, and especially ER+ breast cancer.
ESTROGEN RECEPTOR-MODULATING COMPOUNDS
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Paragraph 000258; 000425, (2019/08/08)
Described herein are compounds that are estrogen receptor modulators of formula I' Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.
TETRAHYDRONAPHTHALENE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF
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Paragraph 0182, (2017/06/06)
Described herein are tetrahydronaphthalene compounds with estrogen receptor modulation activity or function having the Formula I structure: and stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structura
N-heterocyclic carbene-palladium(II)-1-methylimidazole complex catalyzed α-arylation reactions of tetralones with aryl chlorides and further transformation of the products
Yin, Hui-Ying,Lin, Xia-Li,Li, Shu-Wan,Shao, Li-Xiong
, p. 9012 - 9021 (2015/09/01)
NHC-Pd(II)-Im complex 1 has proven to be an efficient catalyst in the reaction between tetralones 2 and aryl chlorides 3, giving the α-arylated tetralones 4 in good to high yields. In addition, if the above reaction mixture was exposed to air at room temp
Palladium-catalyzed α-arylation of arylketones at low catalyst loadings
Marelli, Enrico,Corpet, Martin,Davies, Sian R.,Nolan, Steven P.
supporting information, p. 17272 - 17276 (2015/02/05)
A general catalytic protocol for the α-arylation of aryl ketones has been developed. It involves the use of a preformed, bench-stable Pd-N-heterocyclic carbene pre-catalyst bearing IHept as an ancillary ligand, and allows the coupling of various functiona
Synthetic route for the preparation of substituted 2-phenyl-1,2,3,4-tetrahydronaphthalene-1-ols
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Paragraph 0082, (2013/10/21)
The present invention relates in general to the field of organic chemistry and in particular to the preparation of 2-phenyl-1,2,3,4-tetrahydronaphthalene-1-ol substituted with a protected hydroxyl group. These compounds can be used as intermediates in the
PROCESS FOR THE PREPARATION OF α-SUBSTITUTED KETONES AND THEIR APPLICATION IN SYNTHESIS OF PHARMACEUTICALLY ACTIVE COMPOUNDS
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Page/Page column 20, (2012/12/13)
The present invention relates to a novel one step preparation of 6-methoxy-2-phenyl-tetralone starting from 6-methoxy-tetralone and its use as an intermediate in the synthesis of pharmaceutically active compounds.
Process for the preparation of alfa-substituted ketones and their application in synthesis of pharmaceutically active compounds
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Page/Page column 13, (2012/12/13)
The present invention relates to a novel one step preparation of 6-methoxy-2-phenyl-tetralone starting from 6-methoxy-tetralone and its use as an intermediate in the synthesis of pharmaceutically active compounds.
NEW COMPOUNDS, WHICH ARE POTENT INHIBITORS OF NA/CA EXCHANGE MECHANISM AND ARE USEFUL IN THE TREATMENT OF ARRHYTHMIAS
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Page/Page column 39-40, (2010/02/11)
Therapeutically active compounds of formula (I): wherein X is -O-, -CH2- or -C(O)-; Z is -CHR9- or valence bond; Y is -CH2-, -C(O)-, CH(OR10)-, -CH(NR11R12 )-, -O-, -S-, -S(O)- or -S(O2)-, provided that in case Z is a valence bond, Y is not C(O); the dashed line represents an optional double bond in which case Z is -CR9- and Y is -CH-, C(OR10)- or -C(NR11R12 )-; R1 is -(CH2)nNR4R7 or one of the following groups:n is 1 - 4; R2 and R3 are independently H, lower alkyl, lower alkoxy, -NO2, halogen, -CF3, -OH, -NHR8 or -COOH; R4 and R7 are independently H, lower alkyl or lower hydroxyalkyl; R5 is H, lower alkoxy, -CF3, -NH2 or -CN; R6 is -NO2 , -NR14R19, -CF3 or R8 and R16 are independently H or acyl; R9 is H or lower alkyl; R10 is H, alkylsulfonyl or acyl; R11 and R12 are independently H, lower alkyl or acyl; R13 and R18 are independently H or -OR20; R14 and R19 are independently H, acyl, alkylsulfonyl, C(S)NHR17 or C(O)NHR17; R15 is H or NH2; R17 is H or lower alkyl; R20 is H or acyl; and pharmaceutically acceptable salts and esters thereof are disclosed. The compounds are potent inhibitors of Na/Ca exchange mechanism.
