- Preparation method of 3-(benzyloxy)-1-cyclobutanone
-
The invention relates to the technical field of organic synthesis, and specifically relates to synthesis of a medical intermediate 3-(benzyloxy)-1-cyclobutanone, according to the invention, 3-dibromo-2,3-dibromo-2,3,3-tetramethylpiperidine and diisopropyl malonate are used as initial raw materials; firstly, cyclobutane (I) is obtained through a nucleophilic substitution reaction; deprotection andhydrolysis are carried out on a compound (I) under the action of an acid to obtain 3-oxocyclobutanecarboxylic acid (II), the compound (II) is converted into a carboxylic acid silver salt, a Hunsdiecker reaction is carried out on the carboxylic acid silver salt and elemental bromine to obtain alkyl bromide (III), and a nucleophilic substitution reaction is performed on the compound (III) and benzylalcohol to obtain 3-(benzyloxy)-1-cyclobutanone (IV). The method provides a simple industrial production route for 3-(benzyloxy)-1-cyclobutanone, and has the advantages of simple reaction operation,mild reaction conditions and low cost.
- -
-
Paragraph 0052-0054
(2020/07/12)
-
- Metal-Free sp3 C-SCF3 Coupling Reactions between Cycloketone Oxime Esters and S-trifluoromethyl 4-Methylbenzenesulfonothioate
-
A novel sp3 C-SCF3 coupling reaction between cycloketone oxime esters and S-trifluoromethyl 4-methylbenzenesulfonothioate was achieved. Ethanol was found to facilitate this transformation by trapping the sulfonyl cation. The metal-free and photocatalyst-free reaction conditions, as well as the broad substrate scope, make this a green protocol for the synthesis of SCF3-substituted nitriles.
- Zhao, Xia,Tian, Miaomiao,Ji, Liangshuo,Liu, Junjie,Lu, Kui
-
p. 863 - 866
(2020/02/04)
-
- Synthesis of trisubstituted alkenes by Ni-catalyzed hydroalkylation of internal alkynes with cycloketone oxime esters
-
A method for Ni-catalyzed hydroalkylation of internal alkynes with cycloketone oxime esters was developed. The reaction has a broad substrate scope. This hydroalkylation shows excellent regio-and stereo-selectivity. This method enables readily available starting materials to be used to access a range of cyano-substituted single-configuration trisubstituted alkenes. These are valuable feedstock chemicals and are widely used in synthetic and medicinal chemistry.
- Lu, Xiao-Yu,Liu, Chuang-Chuang,Jiang, Run-Chuang,Yan, Lu-Yu,Liu, Qi-Le,Wang, Qing-Qing,Li, Jia-Mei
-
p. 14191 - 14194
(2020/11/24)
-
- Novel CDK inhibitory compounds, preparation method thereof, pharmaceutical composition for use in preventing or treating CDK relating diseases containing the same as an active ingredient
-
The present invention relates to a novel CDK inhibitory compound, a method for manufacturing the same, and a pharmaceutical composition for preventing or treating a CDK-related disease containing the compound as an active ingredient. The novel CDK inhibit
- -
-
Paragraph 0261-0263; 0265
(2018/10/24)
-
- Multigram Synthesis of C 4/C5 3,3-Difluorocyclobutyl-Substituted Building Blocks
-
An approach for the multigram synthesis of 3,3-difluorocyclobutyl-substituted building blocks (including carboxylic acid, amines, alcohols, azide, trifluoroborate ketone) is described. It is shown that, in most cases, ethyl 3,3-difluorocyclobutanecarboxylate is a convenient common synthetic intermediate to obtain the target derivatives. For preparation of 3,3-difluorocyclobutanol or -cyclobutanone, an alternative pathway via reaction of dichloroketene and tert -butyl or benzyl vinyl ether should be applied.
- Melnykov, Kostiantyn P.,Granat, Dmitriy S.,Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.,Grygorenko, Oleksandr O.
-
p. 4949 - 4957
(2018/12/13)
-
- Copper-Catalyzed Coupling Reactions of Cyclobutanone Oxime Esters with Sulfur Nucleophiles at Room Temperature
-
A copper-catalyzed iminyl radical-mediated C-C bond cleavage/cross-coupling tandem reaction of cyclobutanone oxime esters with aryl thiols in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) at room temperature was developed, and aryl cyanopropyl sulfides were smoothly synthesized in 20-88% yields. By altering the copper reagent and the molar ratio of cyclobutanone oxime ester/aryl thiol/DBU, substitutional product N-arylthio cyclobutanone imines were selectively generated in 50-91% yields. Using this protocol, C-S bond and N-S bond formations using aryl thiols as sulfur sources were realized under very mild conditions without the use of photocatalysis and electrocatalysis techniques.
- He, Mingchuang,Yan, Zhaohua,Zhu, Fuyuan,Lin, Sen
-
p. 15438 - 15448
(2019/01/04)
-
- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
-
This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to halogenated nucleosides optionally conjugated to a phosphorus oxide or pharmaceutically acceptable salts thereof. In certain embodiments, the disclosure relates to conjugate compounds or pharmaceutically acceptable salts thereof comprising an amino acid ester or a sphingolipid or derivative linked by a phosphorus oxide to a nucleotide or nucleoside. In certain embodiments, the disclosure contemplates pharmaceutical compositions comprising these compounds for uses in treating infectious diseases, viral infections, and cancer.
- -
-
Page/Page column 230-231
(2014/08/20)
-
- TRICYCLIC GYRASE INHIBITORS FOR USE AS ANTIBACTERIAL AGENTS
-
Disclosed herein are compounds having the structure of Formula I and pharmaceutically suitable salts, esters, and prodrugs thereof that are useful as antibacterially effective tricyclic gyrase inhibitors. In addition, species of tricyclic gyrase inhibitors compounds are also disclosed herein. Related pharmaceutical compositions, uses and methods of making the compounds are also contemplated.
- -
-
-
- Applications of C-H functionalization logic to cyclobutane synthesis
-
The application of C-H functionalization logic to target-oriented synthesis provides an exciting new venue for the development of new and useful strategies in organic chemistry. In this article, C-H functionalization reactions are explored as an alternative approach to access pseudodimeric cyclobutane natural products, such as the dictazole and the piperarborenine families. The use of these strategies in a variety of complex settings highlights the subtle geometric, steric, and electronic effects at play in the auxiliary guided C-H functionalization of cyclobutanes.
- Gutekunst, Will R.,Baran, Phil S.
-
p. 2430 - 2452
(2014/04/17)
-
- PRECURSOR COMPOUNDS AND METHODS FOR MAKING SAME
-
The present invention relates to a method of obtaining radiopharmaceutical precursors, and in particular precursors to protected amino acid derivatives, which are used as precursors for production of radiolabelled amino acids for use in in vivo imaging procedures, such as positron emission tomography (PET).
- -
-
Paragraph 00059-00061
(2013/03/26)
-
- Investigations into the synthesis, radiofluorination and conjugation of a new [18F]fluorocyclobutyl prosthetic group and its in vitro stability using a tyrosine model system
-
The [18F]fluorocyclobutyl group has the potential to be a metabolically stable prosthetic group for PET tracers. The synthesis of the radiolabeling precursor cis-cyclobutane-1,3-diyl bis(toluene-4-sulfonate) 8 was obtained from epibromohydrin i
- Franck, Dominic,Kniess, Torsten,Steinbach, Joerg,Zitzmann-Kolbe, Sabine,Friebe, Matthias,Dinkelborg, Ludger M.,Graham, Keith
-
p. 643 - 652
(2013/02/25)
-
- Pre-steady state kinetic analysis of cyclobutyl derivatives of 2′-deoxyadenosine 5′-triphosphate as inhibitors of HIV-1 reverse transcriptase
-
Pre-steady state kinetic analysis was utilized for biochemical evaluation of a series of cyclobutyl adenosine nucleotide analogs with HIV-1 RT WT. The phosphonyl-diphosphate form of the cyclobutyl nucleotide, 5, was the most efficiently incorporated of the series. Nucleotide 5 was fourfold more efficiently incorporated than the FDA approved TFV-DP by RTWT. The kinetics of incorporation for 5 using the drug resistant mutant enzyme K65R was also determined. Compound 5 was threefold more efficiently incorporated compared to TFV-DP with RTK65R. These results demonstrate cyclobutyl adenosine analogs can act as substrates for incorporation by HIV-1 RT and be a potential scaffold for HIV inhibitors.
- Kim, Jiae,Wang, Ligong,Li, Yongfeng,Becnel, Kimberlynne D.,Frey, Kathleen M.,Garforth, Scott J.,Prasad, Vinayaka R.,Schinazi, Raymond F.,Liotta, Dennis C.,Anderson, Karen S.
-
supporting information; experimental part
p. 4064 - 4067
(2012/07/14)
-
- PURIFICATION OF PRECURSOR COMPOUND BY CRYSTALLISATION
-
The invention relates to a process for preparation of radiopharmaceutical precursors, and in particular protected amino acid derivatives which are used as precursors for production of radiolabelled amino acids for use in in vivo imaging procedures such as positron emission tomography (PET). Particularly, the invention relates to a process for preparation of a precursor useful in the preparation of the [18F]-1 -amino-3-fluorocyclobutanecarboxylic acid ([18F] FACBC) PET tracer.
- -
-
Page/Page column 11-12
(2012/07/13)
-
- PROCESS SIMPLIFICATION FOR PRECURSOR COMPOUND
-
The invention relates to a process for preparation of radiopharmaceutical precursors, and in particular protected amino acid derivatives which are used as precursors for production of radiolabelled amino acids for use in in vivo imaging procedures such as positron emission tomography (PET). Particularly, the invention relates to a process for preparation of a precursor useful in the preparation of the [18F]-1-amino-3- fluorocyclobutanecarboxyiic acid ([18F] FACBC) PET tracer.
- -
-
Page/Page column 13-14
(2012/07/13)
-
- AZETIDINE AND CYCLOBUTANE DERIVATIVES AS JAK INHIBITORS
-
The present invention relates to azetidine and cyclobutane derivatives, as well as their compositions, methods of use, and processes for preparation, which are JAK inhibitors useful in the treatment of JAK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.
- -
-
Page/Page column 58
(2009/09/28)
-
- BETA-SECRETASE MODULATORS AND METHODS OF USE
-
The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula (I); wherein A, B, W, R3, R4, R5, i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula (I), methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula (I), or compositions including them, to a subject. The invention also comprises further embodiments of Formulas (II) and (III), intermediates and processes useful for the preparation of compounds of the invention.
- -
-
Page/Page column 163
(2010/11/27)
-
- Stereoselective Synthesis of Amino Acid Analogs for Tumor Imaging
-
The radiolabeled non-natural amino acid 1-amino-3-cyclobutane-1-carboxylic acid (ACBC) and its analogs are candidate tumor imaging agents useful for positron emission tomography and single photon emission computed tomography due to their selective affinity for tumor cells. The present invention provides methods for stereo-selective synthesis of syn-ACBC analogs. The disclosed synthetic strategy is reliable and efficient and can be used to synthesize a gram quantity of various syn-isomers of the ACBC analogs, particularly, syn-[18F]-1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC) and syn-[123I]-1-amino-3-iodocyclobutane-1-carboxylic (IACBC) acid analogs.
- -
-
Page/Page column 10
(2010/11/25)
-
- A Versatile Synthesis of Four-, Five-, and Six-membered Cyclic Ketones Using Methyl Methylthiomethyl Sulfoxide
-
Cyclization of 1,n-dihaloalkanes with methyl methylthiomethyl sulfoxide in the presence of a base (n-BuLi or KH) gave three-, four-, five-, and six-membered 1-methylsulfinyl-1-methylthiocycloalkanes.These cyclization products were easily converted to the corresponding ketones by acid hydrolysis except 1-methylsulfinyl-1-methylthiocyclopropane which afforded a complicated mixture.The combination of the cyclization with the acidhydrolysis thus provides a new method for synthesizing four-, five-, and six-membered cycloalkanones.Several representative preparations, such as those of substituted cyclobutanones, 3-cyclopentanone, and tetrahydro-4-pyrone are described.
- Ogura, K.,Yamashita, M.,Suzuki, M.,Furukawa, S.,Tsuchinashi, G.
-
p. 1637 - 1642
(2007/10/02)
-
