A convenient synthesis of hindered amines and α-trifluoromethylamines from ketones

Barney, Charlotte L.; Huber, Edward V.; McCarthy, James R.

doi:10.1016/s0040-4039(00)97893-6

Cited by 80 publications

(30 citation statements)

References 13 publications

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“…Compound 3 was prepared in a one-pot reaction from 1-(3-chlorophenyl)-2-propanone and tert-butylamine using a reductive amination procedure (TiCl 4 /NaCNBH 3 ) developed by Barney et al 9 for the synthesis of hindered amines. The des-chloro analogue 4 was obtained by the simple reaction of α-chloropropiophenone with tert-butylamine using conditions comparable to what we have previously reported for the synthesis of related compounds, and 5 was prepared by a literature method, 10 but isolated as its (previously unknown, and more water-soluble) HCl salt.…”

Section: Synthesismentioning

confidence: 99%

Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release

Shalabi

Walther

Baumann

et al. 2017

ACS Chem. Neurosci.

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Bupropion (1), an α-aminophenone uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET), is a widely prescribed antidepressant and smoking cessation aid. Cathinone (2), a structurally simpler α-aminophenone, is a substrate-type releasing agent at the same transporters and a recognized drug of abuse. Our goal was to identify the structural features of α-aminophenones that govern the mechanistic transition from uptake inhibition to substrate-induced release. Deconstructed analogues of 1 were synthesized and compared for their ability to interact with DAT, NET, and the serotonin transporter (SERT) using in vitro assay methods. Bulky amine substituents resulted in compounds that function as DAT uptake inhibitors but not release agents, whereas smaller amine substituents result in relatively nonselective releasing agents at DAT and NET. Our findings add to empirical evidence supporting distinct molecular determinants for α-aminophenone- (i.e., cathinone-) related agents acting as transporter inhibitors versus those acting as releasers.

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Section: Synthesismentioning

confidence: 99%

Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release

Shalabi

Walther

Baumann

et al. 2017

ACS Chem. Neurosci.

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“…Treatment of 17 with formaldehyde under reductive amination conditions 39 produced the monomethylated compound 25 and the dimethylated analogue 26 (Scheme 7). Reduction of the ketone of 25 and removal of the protecting group afforded 29 .…”

Section: Chemistrymentioning

confidence: 99%

Identification, Synthesis, and Biological Evaluation of the Metabolites of 3-Amino-6-(3′-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6–36), a Promising Rexinoid Lead Compound for the Development of Cancer Chemotherapeutic and Chemopreventive Agents

et al. 2012

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Activation of the retinoid X receptor (RXR), which is involved in cell proliferation, differentiation, and apoptosis, is a strategy for cancer chemotherapy and chemoprevention, and 3amino-6-(3′-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6−36) (3) is among the few RXR ligands known. The presently reported studies of 3 include its binding to human plasma proteins, metabolic stability using human liver microsomes, metabolism by human liver microsomes and hepatocytes, and in vivo disposition in rat serum, liver, and mammary tissue. Compound 3 was 75% bound to human plasma proteins, and its metabolic stability was much greater than propranolol. One phase I metabolite was formed by human liver microsomes, seven phase I and II metabolites were formed by human hepatocytes, and five metabolites were detected in rat serum and liver after oral administration. The putative metabolites predicted using LC-MS-MS were synthesized to confirm their structures and to provide sufficient material for investigation of induction of RXRE transcriptional activity and inhibition of NFκB.

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“…This family of diamines have already been observed in the radical reduction of imines of p-cyanobenzaldehyde 44 by NaTeH 22 or by sodium metal. 28 The monomethylation of amines is a challenge in spite of the number of pathways. 24 This method has been applied to the synthesis of ligand (R,R)and (S,S)-N,N 0 -dimethyl-1,2-diphenylethylene-1,2-diamine on 10 g scale.…”

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confidence: 99%

Reductive amination using a combination of CaH₂ and noble metal

et al. 2015

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Amines were prepared by a reductive amination reaction in the presence of calcium hydride and Pt/C. The in situ formation of water seems to be the key to activate CaH 2 to reduce the intermediate imine.Scheme 1 Reductive amination of cyclohexanone and hexylamine. ; Fax: +33 (0)4 72 43 14 08; Tel: +33 (0)4 72 44 85 07, +33 (0)4 72 43 14 07 † Electronic supplementary information (ESI) available. See

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A convenient synthesis of hindered amines and α-trifluoromethylamines from ketones

Cited by 80 publications

References 13 publications

Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release

Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release

Identification, Synthesis, and Biological Evaluation of the Metabolites of 3-Amino-6-(3′-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6–36), a Promising Rexinoid Lead Compound for the Development of Cancer Chemotherapeutic and Chemopreventive Agents

Reductive amination using a combination of CaH₂ and noble metal

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A convenient synthesis of hindered amines and α-trifluoromethylamines from ketones

Cited by 80 publications

References 13 publications

Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release

Deconstructed Analogues of Bupropion Reveal Structural Requirements for Transporter Inhibition versus Substrate-Induced Neurotransmitter Release

Identification, Synthesis, and Biological Evaluation of the Metabolites of 3-Amino-6-(3′-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11-(6H)dione (AM6–36), a Promising Rexinoid Lead Compound for the Development of Cancer Chemotherapeutic and Chemopreventive Agents

Reductive amination using a combination of CaH2 and noble metal

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Reductive amination using a combination of CaH₂ and noble metal