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Reductive alkylation of hydrazine derivatives with alpha-picoline-borane and its applications to the syntheses of useful compounds related to active pharmaceutical ingredients

An efficient method for the direct reductive alkylation of hydrazine derivatives with alpha-picoline-borane has been developed to synthesize a variety of N-alkylhydrazine derivatives. This method provided N,N-dialkylhydrazine derivatives and N-monoalkylhydrazine derivatives upon fine-tuning of the substrates and the reagent equivalency in a one-pot manner. The method was applied to the synthesis of active pharmaceutical ingredients of therapeutic drugs such as isocarboxazid.

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Piperidine – Wikipedia,
Piperidine | C5H1040N – PubChem

 

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A facile one-pot synthesis of 3-imidazolyl 1,2,4-triazoles and 1,2,4-oxa-diazolones

5-(5-Aminoimidazol-4-yl)-1,2,4-triazol-3-ones were obtained under mild experimental conditions from 5-amino-4-(N-ethoxycarbonyl) cyanoformimidoyl imidazoles and hydrazine in a rapid one-pot reaction. When hydroxylamine hydrochloride was used, in the presence of base, the corresponding 1,2,4-oxadiazol-5-ones were isolated. An equally fast reaction occurred when 5-amino-4-(N-acetyl/benzoyl) cyanoformimidoyl imidazoles were combined with hydrazine to give 5-(5-aminoimidazol-4-yl)-1,2,4-triazoles.

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SULPHUR CONTAINING PYRAZOLE DERIVATIVES AS SELECTIVE CANNABINOID CB1 RECEPTOR ANTAGONISTS

The present invention relates to sulphur containing pyrazole derivatives, and their S-oxidized active metabolites, as selective cannabinoid CB1 receptor antagonists having a high CB1/CB2 receptor subtype selectivity, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of these pyrazole derivatives, to pharmaceutical compositions comprising one or more of these pyrazole derivatives as active ingredients, as well as to the use of these pharmaceutical compositions for the treatment of psychiatric and neurological disorders. The compounds have the general formula (I)wherein the symbols have the meanings given in the specification.

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4,5-DIPHENYLIMIDAZOLES FROM THE CYCLIZATION OF BENZIL N-ALKYLMONOHYDRAZONES

The thermal cyclization of monodisubstituted hydrazones (1) affords the corresponding N-substituted-4,5-diphenylimidazoles in good to excellent yields; possible mechanisms for this unusual cyclization are presented.

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Synthesis, structures, and DFT bonding analysis of new titanium hydrazido(2-) complexes

The reaction of 1,1-diphenylhydrazine with Ti(NMe2) 2Cl2 produced the monomeric terminal titanium hydrazido(2-) species Ti(NNPh2)Cl2(HNMe2) 2 (1) in near-quantitative yield. The reaction of Ti(NMe 2)2Cl2 with the less sterically demanding ligand precursors 1,1-dimethylhydrazine or N-aminopiperidine gave the dimeric mu-eta2,eta1-bridged compounds Ti 2(mu-eta2,eta1-NNMe2) 2Cl4(HNMe2)2 (2) and Ti 2{mu-eta2,eta1-NN(CH2) 5}2Cl4(HNMe2)3 (3). The X-ray structures of 2 and 3 showed the formation of N-H…Cl hydrogen bonded dimers or chains, respectively. The reaction of 1 with an excess of pyridine formed [Ti(NNPh2)Cl2(py)2]n (4, n = 1 or 2). The reaction of the tert-butyl imido complex Ti(N tBu)Cl2(py)3 with either 1,1-dimethylhydrazine or N-aminopiperidine again resulted in the formation of hydrazido-bridged dimeric complexes, namely Ti2(mu-eta2, eta1-NNMe2)2Cl4(py)2 (5, structurally characterized) and Ti2{mu-eta2, eta1-NN(CH2)5}2Cl 4(py)2 (6). Compounds 1 and 4 are potential new entry points into terminal hydrazido(2-) chemistry of titanium. Compound 1 reacted with neutral fac-N3 donor ligands to form Ti(NNPh2)Cl 2(Me3[9]aneN3) (7), Ti(NNPh2)Cl 2(Me3[6]aneN3) (8), Ti(NNPh2)Cl 2{HC(Me2pz)3} (9, structurally characterized), and Ti(NNPh2)Cl2{HC(nBupz)3} (10) in good yields (Me3[9]aneN3 = trimethyl-1,4,7- triazacyclononane, Me3[6]aneN3 = trimethyl-1,3,5- triazacyclohexane, HC(Me2pz)3 = tris(3,5- dimethylpyrazolyl)methane, and HC(nBupz)3 = tris(4- nbutylpyrazolyl)-methane). DFT calculations were performed on both the model terminal hydrazido compound Ti(NNPh2)Cl2{HC(pz) 3} (I) and the corresponding imido compounds Ti(NMe)Cl 2{HC(pz)3} (II) and Ti(NPh)Cl2{HC(pz) 3} (III). The NNPh2 ligand binds to the metal center in an analogous manner to that of terminal imido ligands (metal?ligand triple bond), but with one of the Ti=Nalpha pi components significantly destabilized by a pi* interaction with the lone pair of the N beta atom. The NR ligand sigma donor ability was found to be NMe > NPh > NNPh2, whereas the overall (sigma + pi) donor ability is NMe > NNPh2 > NPh, as judged by fragment orbital populations, Ti-N atom-atom overlap populations, and fragment-charge analysis. DFT calculations on the hydrazido ligand in a mu-eta2, eta1-bridging mode showed involvement of the N=N pi electrons in donation to one of the Ti centers. This TiN2 interaction is best represented as a metallocycle.

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NOVEL IMIDAZO[1,2-a]PYRIDINE CANNABINOID RECEPTOR LIGANDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

The present invention relates to novel imidazo[1,2-a]pyridine cannabinoid receptor ligands, in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2) receptor ligands, and uses thereof for treating diseases, conditions and/or disorders modulate by a cannabinoid receptors (such as pain, neurodegenerative disorders, eating disorders, weight loss or control, obesity and diabetes).

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Tricyclic pyrazoles: An efficient approach to cannabinoid analogues with a tricyclic framework incorporating the pyrrole and pyrazole moieties

In this paper we report the synthesis of some new cannabinoid analogues that share with rimonabant, a potent and selective CB1 antagonist, the 2,4-dichlorophenyl and piperidin-1-yl substituents on the pyrazole and amide nitrogens, respectively. The general synthesis involves the preparation of a cyclic ketone condensed with a pyrrole, followed by Claisen condensation with diethyl oxalate; from here, an aza-annulation reaction with a substituted hydrazine followed by an amidation step complete the synthesis. Georg Thieme Verlag Stuttgart.New York.

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Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors

Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of mu-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at subeffective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH2. The bivalent compound (9) has been used for in vitro binding assays, for in vivo antinociception models and in vitro hypothalamic perfusion test, to evaluate the neurotransmitters release.

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A general and mild domino approach to substituted 1-aminoindoles

A versatile and efficient palladium catalyzed domino reaction leading to a broad range of substituted 1-aminoindoles has been developed. The title compounds were prepared from 2-halo-phenylacetylenes and simple hydrazines in good to excellent yields in just a few hours under mild conditions.

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Synthesis of novel pyrido[2,3-e][1,3]oxazines

The preparation of novel pyrido[2,3-e][1,3]oxazines starting from 3-hydroxy-pyridine-2-carbonitrile, N-aralkoxy-3-hydroxy-pyridine-2-carboxamides and 3-hydroxy-pyridine-2-carboxylic acid hydrazides is described.

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