20912-56-5Relevant academic research and scientific papers
One-pot synthesis of primary tert-alkylamines by the addition of organometallic reagents to nitriles mediated by Ti(Oi-Pr)4
Tomashenko, Olesya,Sokolov, Viktor,Tomashevskiy, Alexander,De Meijere, Armin
, p. 652 - 654 (2007)
A number of primary tert-alkylamines (18 examples, 25-72% yields) have been prepared according to a simple one-pot procedure by the addition of organometallic reagents such as Grignard reagents and organolithium compounds to nitriles in the presence of Ti(Oi-Pr)4. Georg Thieme Verlag Stuttgart.
Iodine-mediated 1,2-aryl migration of primary benzhydryl amines
Chang, Junbiao,Du, Yangxu,Hao, Wei,Hou, Jiao,Lu, Qing,Yu, Wenquan
supporting information, p. 16223 - 16226 (2021/09/22)
An iodine-mediated 1,2-aryl migration reaction of primary benzhydryl amines under transition metal-free conditions has been achieved. The crude imines generated by this rearrangement reaction can be directly transformed into various aromatic secondary ami
Enantioselective Access to 1H-Isoindoles with Quaternary Stereogenic Centers by Palladium(0)-Catalyzed C?H Functionalization
Grosheva, Daria,Cramer, Nicolai
supporting information, p. 13644 - 13647 (2018/09/27)
A catalytic enantioselective method for the synthesis of chiral 1H-isoindoles bearing quaternary stereogenic centers is reported. Powered by readily accessible phosphordiamidite ligands, the presented palladium(0)-catalyzed C?H functionalization uses trifluoroacetimidoyl chlorides as electrophilic components. It delivers previously inaccessible perfluoroalkylated 1H-isoindoles in high yields and enantioselectivities. The subsequent diastereoselective addition of nucleophiles provides access to densely substituted and sterically hindered isoindolines.
Convergent Synthesis of Diverse Nitrogen Heterocycles via Rh(III)-Catalyzed C-H Conjugate Addition/Cyclization Reactions
Weinstein, Adam B.,Ellman, Jonathan A.
supporting information, p. 3294 - 3297 (2016/07/13)
The development of Rh(III)-catalyzed C-H conjugate addition/cyclization reactions that provide access to synthetically useful fused bi- and tricyclic nitrogen heterocycles is reported. A broad scope of C-H functionalization substrates and electrophilic olefin coupling partners is effective, and depending on the nature of the directing group, cyclic imide, amide, or heteroaromatic products are obtained. An efficient synthesis of a pyrrolophenanthridine alkaloid natural product, oxoassoanine, highlights the utility of this method.
Rapid Ti(Oi-Pr)4 facilitated synthesis of α,α,α-trisubstituted primary amines by the addition of Grignard reagents to nitriles under microwave heating conditions
Wang, Ruifang,Gregg, Brian T.,Zhang, Wei,Golden, Kathryn C.,Quinn, John F.,Cui, Peng,Tymoshenko, Dmytro O.
experimental part, p. 7070 - 7073 (2010/03/01)
A series of carbinamines (α,α,α-trisubstituted amines) have been prepared in a simple and efficient one-pot procedure by the addition of Grignard reagents to a series of aliphatic, aromatic and heteroaromatic nitriles. The resulting magnesium imines are subsequently converted to the desired amine after treatment with Ti(Oi-Pr)4 and additional microwave heating. Key to this procedure is the use of microwave heating for both steps of the reaction protocol, which significantly improves both reaction yields and reduces reaction times. In general, the Grignard addition reaction is complete within 5-10 min at 100 °C followed by conversion with Ti(Oi-Pr)4 and additional microwave heating to give the target amines in good yields.
Syntheses and reactions of 1-amino-2,2-dialkylcyclopropane-1- carbonitriles and -carboxamides - Potential precursors of ACC derivatives
Aelterman, Wim,Tehrani, Kourosch Abbaspour,Coppens, Wim,Huybrechts, Tom,De Kimpe, Norbert,Tourwe, Dirk,Declercq, Jean-Paul
, p. 239 - 250 (2007/10/03)
The direct cyclization of 2-amino-4-chloro,3,3-dimethylbutanenitrile with potassium tert-butoxide in THF afforded 1-amino-2,2- dimethylcyclopropane-1-carbonitrile and a dimerization product. Various new cis- and trans-1-(tert-butylamino)-2-benzyl-2-methylcyclopropane- carbonitriles and the corresponding cyclopropanecarboxamides have been synthesized, with focus on the isolation of the pure stereoisomeric cyclopropanecarboxamides. The relative configuration of the stereoisomers was established by X-ray crystallographic analysis of one of the model compounds. A new route to the latter functionalized cyclopropanes was developed by reaction of 1-methoxycyclopropylamines with potassium cyanide. Some remarkable rearrangements of 1-aminocyclopropane-1-carbonitriles into azetidine and oxazine derivatives via Favorskil-derived intermediates are reported. Various aspects of the chemistry of geminally functionalized cyclopropanes are discussed.
N-cumyl benzamide, sulfonamide, and aryl O-carbamate directed metalation groups. Mild hydrolytic lability for facile manipulation of directed ortho metalation derived aromatics
Metallinos, Costa,Nerdinger, Sven,Snieckus, Victor
, p. 1183 - 1186 (2008/02/09)
(Matrix Presented) N-Cumyl benzamide (2), sulfonamide (8), and O-carbamate (11) compounds undergo directed ortho metalation under standard conditions to give, after quench with a variety of electrophiles, the substituted products 3, 9, and 12, respectively. Regiospecific and convenient approaches to phthalimides (7), 1,2-benzisothiazole 1,1-dioxides (10b), and ortho-substituted phenols (13a) and salicylamides (13b) are thereby established The mild deprotection protocol for these new cumyl directed metalation groups (DMGs) suggests that they will supersede previous corresponding groups for synthetic anionic aromatic chemistry.
1,2-Radical Rearrangements of Aryl, Furanyl and Thiophenyl Groups from Carbon to Nitrogen
Kim, Sunggak,Do, Jung Yun
, p. 1607 - 1608 (2007/10/02)
1,2-Radical rearrangements of aryl, furanyl and thiophenyl groups from carbon to nitrogen using azido groups as radical precursors are observed for the first time; the 1,2-aryl rearrangement is applied to the synthesis of phenanthridine derivatives from 6-fluorenyl azides.
(2-Alkyl-3-pyridyl)methylpiperazine derivatives as PAF antagonists
-
, (2008/06/13)
The present invention relates to new (2-alkyl-3-pyridyl) methylpiperazine derivatives of general formula I: wherein R1, R2 and Z are as defined in Claim 1. The invention also relates to processes for their preparation and to pharmaceutical compositions containing them. These compounds are potent, orally active PAF antagonists and, consequently, they are useful in the treatment of the diseases in which this substance is involved.
Synthesis and Structure-Activity Relationships of 1-Acyl-4-(2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF Antagonists
Carceller, Elena,Merlos, Manuel,Giral, Marta,Almansa, Carmen,Bartroli, Javier,et al.
, p. 2984 - 2997 (2007/10/02)
A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines, with increased oral activity was prepared and evaluated in vitro in PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP).Oral activity was ascertained through a PAF-induced mortality test in mice (MOR).Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test.Three different types of acylsubstituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups.The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 μM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR-12519, PAG IC50 = 0.041 μM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086.Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests.On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.
