- Synthesis method of N-benzyl-4-piperidine formaldehyde
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The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of N-benzyl-4-piperidine formaldehyde. According to the invention, 4-piperidinecarboxylic acid is used as a raw material; an esterification reaction is carried out to generate 4-methyl piperidinecarboxylate hydrochloride; an alkylation reaction is carried out on N-benzyl-4-methyl piperidinecarboxylate hydrochloride to generate N-benzyl-4-methyl piperidinecarboxylate; n-benzyl-4-methyl piperidinecarboxylate is hydrolyzed to obtain N-benzyl-4-piperidinecarboxylic acid, N-benzyl-4-piperidinecarboxylic acid is subjected to an acylation reaction to generate N-benzyl-4-piperidinecarboxamide, N-benzyl-4-piperidinecarboxamide is dehydrated to obtain 1-benzylpiperidine-4-nitrile, and 1-benzylpiperidine-4-nitrile is subjected to a reduction reaction to generate N-benzyl-4-piperidineformaldehyde. The method is mild in reaction condition, simple in aftertreatment and high in yield, N-benzyl-4-piperidinecarboxaldehyde can be obtained at the high yield at the temperature of 0 DEG C, column chromatography is not needed, and repeatability is high.
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Paragraph 0030; 0039-0040
(2020/08/18)
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- Preparation of Indolenines via Nucleophilic Aromatic Substitution
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An unusual aromatic substitution to access indolenines is described. 2-(2-Methoxyphenyl)acetonitrile derivatives are reacted with various alkyl and aryl Li reagents to furnish the corresponding indolenine products, constituents of natural products, and cyanine dyes such as indocyanine green. This new method was used to synthesize 41 indolenines with large functional group tolerance, and selected examples were further converted to the corresponding indolenine dyes. Key experiments provide insight into the mechanism of this nucleophilic aromatic substitution.
- Huber, Florian,Roesslein, Joel,Gademann, Karl
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supporting information
p. 2560 - 2564
(2019/03/19)
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- Copper-Catalyzed Alkylation of Nitroalkanes with α-Bromonitriles: Synthesis of β-Cyanonitroalkanes
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Copper catalysis now enables the efficient C-alkylation of nitroalkanes with α-bromonitriles. Using a simple and inexpensive catalyst, this process provides access to β-cyanonitroalkanes. The method is highly tolerant of various functional groups and substitution patterns. These functionally dense products serve as orthogonally masked 1,3-diamines, which can be revealed selectively for access to differentially substituted diamines. These products can also be exploited for the formation of complex cyanoalkenes and 5-aminoisoxazoles.
- Shimkin, Kirk W.,Gildner, Peter G.,Watson, Donald A.
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supporting information
p. 988 - 991
(2016/03/15)
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- Synthesis of Nitriles from Aldoximes and Primary Amides Using XtalFluor-E
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The dehydration reaction of aldoximes and amides for the synthesis of nitriles using [Et2NSF2]BF4 (XtalFluor-E) is described. Overall, the reaction proceeds rapidly (normally 1 h) at room temperature in an environmentally benign solvent (EtOAc) with only a slight excess of the dehydrating agent (1.1 equiv). A broad scope of nitriles can be prepared, including chiral nonracemic ones. In addition, in a number of cases, further purification of the nitrile after the workup was not required.
- Keita, Massaba,Vandamme, Mathilde,Paquin, Jean-Fran?ois
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p. 3758 - 3766
(2015/11/28)
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- Synthesis of the pleuromutilin antibiotic SB-268091: A new practical and efficient synthesis of quinuclidine-4-thiol
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A synthesis of the pleuromutilin antibiotic SB-268091 is described which includes a new and improved route to the quinuclidine-4-thiol ligand. This chemistry has been run on multikilo scale and involved a reductive double debenzylation using sodium in liquid ammonia. Alternative conditions have been developed to prepare quinuclidine-4-thiol which avoid the use of sodium in liquid ammonia. The generality of this process to prepare differentially S-protected quinuclidine-4-thiols is also discussed and exemplified by the preparation of a range of analogues.
- Choudary, Bernie,Giles, Robert G.,Jovic, Florence,Lewis, Norman,Moore, Steve,Urquhart, Michael
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p. 1927 - 1939
(2013/03/13)
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- Heteroatom-directed alkylcyanation of alkynes
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Alkanenitriles having a heteroatom such as nitrogen, oxygen, and sulfur at the γ-position are found to add across alkynes stereo-and regioselectively by nickel/Lewis acid catalysis to give highly substituted acrylonitriles. The heteroatom functionalities likely coordinate to the nickel center to make oxidative addition of the C-CN bonds of the alkyl cyanides kinetically favorable, forming a five-membered nickelacycle intermediate and, thus, preventing β-hydride elimination to allow the alkylcyanation reaction.
- Nakao, Yoshiaki,Yada, Akira,Hiyama, Tamejiro
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supporting information; experimental part
p. 10024 - 10026
(2010/10/04)
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- OCTAHYDROPYRROLO [3, 4-C] PYRROLE DERIVATIVES AN THEIR USE AS ANTIVIRAL AGENTS
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Chemokine receptor antagonists, in particular, 3,7-diazabicyclo [3.3.0] octane compounds according to formula (I) wherein R1-R3 and Ar are as defined herein are antagonists of chemokine CCR5 receptors which are useful for treating or preventing an human immunodeficiency virus (HIV) infection, or treating AIDS or ARC. The invention further provides methods for treating diseases that are alleviated with CCR5 antagonists. The invention includes pharmaceutical compositions and methods of using the compounds for the treatment of these diseases. The invention further includes processes for the preparation of compounds according to formula (I).
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Page/Page column 40; 66
(2008/06/13)
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- 5-HTX MODULATORS
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This invention relates to compounds which bind to serotonin receptors inside or outside the central nervous system, in particular compounds which bind to the 5-HT2 or 5-HT7 receptors, their preparation and use, compositions containing them, and methods of treatment using them.
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Page/Page column 53-54
(2008/06/13)
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- MODULATORS OF PERIPHERAL 5-HT RECEPTORS
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Novel modulators of 5-HT4 receptors have been developed which have a selectivity for peripheral receptors rather than those of the central nervous systems. Theses include novel derivatives of known modulators as well as entirely novel entities. Surprisingly, the derivatised compounds of the known modulators maintain a high binding affinity to 5-HT4 receptors, despite the presence of an acidic moiety at the end of an optional chain. The entirely novel entities also exhibit good binding affinity to 5-HT4 receptors. All of the compounds of the invention have a common motif which includes a basic nitrogen moiety and an acidic moiety. The compounds of the invention, due at least in part to their high ionisation potential at physiological pH, have the unique properties of selectively for peripheral 5HT4 receptors over those of the CNS, good binding affinity, and selectively of 5HT4 receptors over other serotonin receptors.
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Page/Page column 52
(2010/02/12)
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- SUBSTITUTED 3- AND 4- AMINOMETHYLPIPERIDINES FOR USE AS BETA-SECRETASE IN THE TREATMENT OF ALZHEIMER’S DISEASE
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The invention relates to novel compounds, which are substituted chiral or achiral derivatives of 3- or 4- aminomethylpiperidine of the general formula (I). The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of general formula (I) and especially their use as inhibitors of beta-secretases for the treatment of Alzheimer’s disease.
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Page/Page column 21; 42-43; 45
(2008/06/13)
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- Phthalazine derivatives and remedies for erectile dysfunction
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The present invention provides a phthalazine compound as a therapeutic agent for erectile dysfunction represented by the following formula, a pharmacologically acceptable salt thereof or a hydrate thereof: wherein R1and R2are the same as or different from each other and represent a halogen atom, a C1 to C4 alkyl group which may be substituted with a halogen atom, a C1 to C4 alkoxy group which may be substituted with a halogen atom or a cyano group; X represents a cyano group, a nitro group, a halogen atom, a hydroxyimino group which may be substituted or a heteroaryl group which may be substituted; Y represents a heteroaryl group, an aryl group which may be substituted, an alkynyl group which may substituted, an alkenyl group, an alkyl group, an optionally substituted saturated or unsaturated 4- to 8-membered amine ring, and the cyclic amine compound is a monocyclic compound, bicyclic compound or a spiro compound; l is an integer of 1 to 3; provided that the case where l is 1 or 2, X is a cyano group, a nitro group or a chlorine atom, R1is a chlorine atom, R2is a methoxy group and Y is a 5- or 6-membered amine ring substituted with a hydroxyl group is excluded.
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- Cyano Phosphate: An Efficient Intermediate for the Chemoselective Conversion of Carbonyl Compounds to Nitriles
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Cyanohydrin diethyl phosphates, readily obtained from various ketones and aldehydes by reaction with diethyl phosphorocyanidate and lithium cyanide, reacted chemoselectively with samarium(II) iodide in THF to give the corresponding nitriles in excellent yields.This method was also found applicable to α,β-unsaturated carbonyl compounds via cyano phosphates to give β,γ-unsaturated nitriles, not obtainable by standard methods, without isomerization of the double bonds.
- Yoneda, Ryuji,Harusawa, Shinya,Kurihara, Takushi
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p. 1827 - 1832
(2007/10/02)
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- CYANOPHOSPHATE: AN EFFICIENT INTERMEDIATE FOR CONVERSION OF CARBONYL COMPOUNDS TO NITRILES
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A novel and high yield conversion of saturated or unsaturated carbonyl compounds to nitriles via cyanophosphates by samarium diiodide in the presence of tert-butanol is described.
- Yoneda, Ryuji,Harusawa, Shinya,Kurihara, Takushi
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p. 3681 - 3684
(2007/10/02)
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- Synthesis and antihypertensive activity of some new quinazoline derivatives
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A series of substituted 2-piperidino-4-amino-6,7-dimethoxyquinazolines was synthesized and screened as potential antihypertensive agents. The hypotensive effect of all the new compounds was studied after intravenous administrations in urethane-anesthetized normotensive rats. The furoylpiperazine moiety in the prazosin molecule could be replaced by a more stable substituted piperidine group without loss of the blood pressure lowering activity. However, the nature of the substituent profoundly influenced the hypotensive potency as well as the duration of the hypotensive action. Some of the new compounds were found to be as potent as prazosin. On the basis of potency and the duration of the hypotensive action in the anesthetized rats, five of the most promising compounds were selected for further studies. Each of these agents exerted an antihypertensive effect upon oral administrations in conscious spontaneously hypertensive rats. At small doses, the new compounds appeared to be somewhat less potent than prazosin, but at the higher doses of 10-100 μmol/kg, two of them appeared to be even more efficacious antihypertensive agents than prazosin.
- Honkanen,Pippuri,Kairisalo,Nore,Karppanen,Paakkari
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p. 1433 - 1438
(2007/10/02)
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