73286-70-1Relevant articles and documents
Preparation method of medical intermediate N-BOC-3-pyrroline
-
Paragraph 0065; 0068-0069; 0072-0073; 0076, (2021/07/31)
The invention discloses a preparation method of a medical intermediate N-BOC-3-pyrroline. The method comprises the following steps: adding a proper amount of benzylamine, 3-bromopropylene, dichloromethane and an alkaline reagent into a reaction bottle for reaction to obtain an enamine compound; dissolving the enamine compound in dichloromethane, adding a catalyst (Grubbs first generation) for reaction, adding anhydrous sodium sulfate after adding water for layering, and performing suction filtration to obtain mother liquor; adding 1-chloroethyl chloroformate and methanol into the mother liquor, debenzylating to obtain pink solid, adding petroleum ether into the pink solid, pulping, and carrying out suction filtration to obtain 3-pyrroline hydrochloride; and re-dissolving the 3-pyrroline hydrochloride with water, adding an alkaline solution of NaHCO3 and (BOC)2O, stirring and reacting, extracting after the reaction is finished, separating out an organic phase, and drying to obtain a finished product of N-BOC-3-pyrroline. The method is low in raw material cost, simple in process step, high in yield, small in pollution, high in product purity and suitable for industrial production.
Merging Halogen-Atom Transfer (XAT) and Cobalt Catalysis to Override E2-Selectivity in the Elimination of Alkyl Halides: A Mild Route towardcontra-Thermodynamic Olefins
Zhao, Huaibo,McMillan, Alastair J.,Constantin, Timothée,Mykura, Rory C.,Juliá, Fabio,Leonori, Daniele
supporting information, p. 14806 - 14813 (2021/09/18)
We report here a mechanistically distinct tactic to carry E2-type eliminations on alkyl halides. This strategy exploits the interplay of α-aminoalkyl radical-mediated halogen-atom transfer (XAT) with desaturative cobalt catalysis. The methodology is high-yielding, tolerates many functionalities, and was used to access industrially relevant materials. In contrast to thermal E2 eliminations where unsymmetrical substrates give regioisomeric mixtures, this approach enables, by fine-tuning of the electronic and steric properties of the cobalt catalyst, to obtain high olefin positional selectivity. This unprecedented mechanistic feature has allowed access tocontra-thermodynamic olefins, elusive by E2 eliminations.
A Scalable Membrane Pervaporation Approach for Continuous Flow Olefin Metathesis
Breen, Christopher P.,Parrish, Christine,Shangguan, Ning,Majumdar, Sudip,Murnen, Hannah,Jamison, Timothy F.,Bio, Matthew M.
supporting information, p. 2298 - 2303 (2020/05/14)
The translation of olefin metathesis reactions from the laboratory to process scale has been challenging with traditional batch techniques. In this contribution, we describe a continuous membrane reactor design that selectively permeates the ethylene byproduct from metathetical processes, thereby overcoming the mass-transport limitations that have negatively influenced the efficiency of this transformation in batch vessels. The membrane sheet-in-frame pervaporation module yielded turnover numbers of >7500 in the case of diethyl diallylmalonate ring-closing metathesis. The preparation of more challenging, low-effective-molarity substrates, a cyclooctene and a 14-membered macrocyclic lactone, was also effective. A comparison of optimal membrane reactor conditions to a sealed tubular reactor revealed that the benefits of ethylene removal are most apparent at low reaction concentrations.
JAK inhibitor compound and application thereof
-
Paragraph 0508; 0515; 0526-0527, (2020/09/12)
The invention relates to a JAK inhibitor compound and application thereof. Specifically, the invention discloses a compound shown as a formula (G), or an isotope labeled compound, or an optical isomer, a geometrical isomer, a tautomer or an isomer mixture of the compound, or a pharmaceutically acceptable salt of the compound, or a prodrug of the compound, or a metabolite of the compound. The invention also relates to the medical application of the compound.
Synthesis of new (±)-1-(4-(3-fluorobenzyloxy)pyrrolidin-3-yl)-4-phenyl-1H-1,2,3-triazole derivatives via click reaction and study of anti-cancer activity against HCT 116, MDA-MB231, Mia-PaCa2 cell lines
Kumar, Gollapudi Ravi,Murthy Boddapati,Meruga, Santha Kumari,Bollikolla, Hari Babu
, p. 2813 - 2825 (2020/10/06)
ASERIES of 16 new (±) -1-(4-(3-fluorobenzyloxy) pyrrolidin-3-yl)-4-phenyl-1H-1,2,3-triazole derivatives were synthesized from 2,5-dihydro-1H-pyrrole. Sixteen compounds are well characterized by their 1H NMR, 13C NMR and mass spectral data. Anticancer activities of these compounds were tested against HCT 116, MDA-MB231, Mia-PaCa2 cancer cell lines. Among these series of compounds, 8b exhibited highest activity with IC50 of 42.5 μg/ mL against MDA-MB231 cell line. The compound 8o and 8n showed moderate activity with IC50 of 64.3 μg/ mL and 68.4 μg/ mL against HCT -116 and Mia-PaCa2 cancer cell lines respectively.
Discovery of 1-pyrimidinyl-2-aryl-4,6-dihydropyrrolo [3,4-d]imidazole-5(1H)-carboxamide as a novel JNK inhibitor
Cho, Hyunwook,Hah, Jung-Mi,Im, Daseul,Jang, Miyoung,Moon, Hyungwoo,Oh, Youri,Yang, Songyi
, (2020/03/13)
We designed and synthesized 1-pyrimidinyl-2-aryl-4, 6-dihydropyrrolo [3,4-d] imidazole-5(1H)-carboxamide derivatives as selective inhibitors of c-Jun-N-terminal Kinase 3 (JNK3), a target for the treatment of neurodegenerative diseases. Based on the compounds found in previous studies, a novel scaffold was designed to improve pharmacokinetic characters and activity, and compound 18a, (R)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydro pyrrolo [3,4-d]imidazole-5(1H)-carboxamide, showed the highest IC50 value of 2.69 nM. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases, having mild activity against JNK2, RIPK3, and GSK3β, which also known to involve in neuronal apoptosis.
NOVEL HETEROCYCLIC COMPOUNDS AS IRAK4 INHIBITORS
-
Page/Page column 32, (2019/06/23)
The present invention relates to novel compounds of the general formula (I) their tautomeric forms, their enantiomers, their diastereoisomers, their pharmaceutically accepted salts, or pro-drugs thereof, which are useful for the treatment or prevention of cancer and inflammatory diseases associated with Interleukin-1 Receptor Associated Kinase (IRAK), and more particularly compounds that modulate the function of IRAK4.
N-Heterocyclic Carbene Complexes Of Metal Imido Alkylidenes And Metal OXO Alkylidenes, And The Use Of Same
-
Paragraph 0154, (2017/03/21)
The invention relates to an N-heterocyclic carbene complex of general formulas I to IV (I) (II) (III) (IV), according to which A1 stands for NR2 or PR2, A2 stands for CR2 R2′, NR2, PR2, 0 or S, A3 stands for N or P, and C stands for a carbene carbon atom, ring B is an unsubstituted or a mono or poly-substituted 5 to 7-membered ring, substituents R2 and R2′ stand, inter alia, for a linear or branched C1-Cw-alkyl group and, if N and N each stand for NR2 or PR2, are the same or different, M in formulas I, II, III or IV stands for Cr, Mo or W, X 1 or X2 in formulas I to IV are the same or different and represent, inter alia, C1-C1s carboxylates and C1-C1s-alkoxides, Y is inter alia oxygen or sulphur, Z is inter alia a linear or branched C1-Cw-alkylenoxy group, and R 1 and R1′ in formulas I to IV are, inter alia, an aliphatic or aromatic group. These compounds are particularly suitable for use as catalysts for olefin metathesis reactions and have the advantage, compared to known Schrock carbene complexes, of displaying clearly increased tolerance to functional groups such as, in particular, aldehydes, secondary amines, nitriles, carboxylic acids and alcohols.
SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
-
Page/Page column 804, (2018/01/20)
The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
A short synthesis of pyridines from deprotonated α-aminonitriles by an alkylation/RCM sequence
Weber, Carina,Nebe, Marco M.,Kaluza, Lukas P. V.,Opatz, Till
, p. 633 - 641 (2016/07/06)
α-Aminonitriles can serve as versatile key precursors for the synthesis of nitrogen containing heterocycles. After unsuccessful trials involving the [1,2]-Stevens rearrangement of nitrile-stabilized ammonium ylides, we herein report a simple three-step synthesis of substituted pyridines based on an alkylation/ring-closing metathesis/aromatization sequence.
