84702-73-8

Upstream product

• 5891-21-4 5-chloro-2-pentanone 
• 13483-31-3 Acetone dimethylhydrazone 
• 42059-30-3 1-azido-2-iodoethane 
• 517-23-7 3-acetyl-2-oxo-4,5-dihydrofuran 
• 3884-71-7 bromo-5-pentanone-2 

Downstream Products

• 113738-73-1 Cyclohexyl-[3-(2-methyl-[1,3]dithiolan-2-yl)-propyl]-amine; hydrochloride 
• 872-32-2 2-methyl-1H-pyrroline 
• 186303-33-3 1-(R)-(3.4-dihydroxyphenyl)-2-(1-methyl-4-azidobutylamino)ethanol oxalate salt 

Relevant academic research and scientific papers

Convenient Cyclopentadiene Modifications for Building Versatile (Radio-)Metal Cyclopentadienyl Frameworks

The synthesis of a bifunctional cyclopentadiene-based building block, bearing an alkyl linker with a terminal chloride and an ester group is described. This building block was modified by nucleophilic substitution, leading to two new fac-[Re(CO)3]+ containing derivatives of known drug candidates for brain imaging and multi-drug resistance in cancer in as few as two steps. Furthermore, the chloride was replaced by an azide, which was subsequently coupled to phenylacetylene as a model alkyne to demonstrate its versatility for undergoing Click-type reactions. The resulting triazole was labelled with 99mTc to yield the corresponding piano-stool complex in a radiochemical purity of 86 %. The identities were confirmed by coinjection with the Re homologue.

Solid-phase organic synthesis of unnatural polyamine analogues bearing a dansyl or acridine moiety

The synthesis of unnatural polyamines and polyamine conjugates from a protected triamine anchored to Wang resin is described. The use of solid-phase organic synthesis for such hydrophilic compounds is of interest because it removes the need for often awkward chromatographic purification of intermediates and is easily applied to the synthesis of compound libraries. Chain elongation was achieved by reductive amination and the resulting resin bound tetraamine was functionalized with dansyl and acridine moieties. The conjugates were cleaved from the resin and these studies should lead to the rapid synthesis of libraries for biological evaluation.

Synthesis of Pyrrolidines by a Csp3-Csp3/Csp3-N Transition-Metal-Free Domino Reaction of Boronic Acids with γ-Azido-N-Tosylhydrazones

The reaction between γ-azido-N-tosylhydrazones and boronic acids leads to the obtention of 2,2-disubstituted pyrrolidines in a domino process that includes 1) diazoalkane formation, 2) intermolecular carboborylation of the diazocompound, and 3) intramolecular carborylation of the azide, and comprises the formation of a Csp3?Csp3 and a Csp3?N bonds on the same carbon atom. The reaction proceeds without the need of any transition-metal catalyst under microwave activation and features wide scope in both reaction partners. It can be applied to both alkyl and arylboronic acids with equal efficiency. With N-tosylhydrazones derived from 2-(2-azidoethyl)-cyclopentanone and cyclohexanone the reactions are highly diastereoselective leading to the cis-fused bicyclic systems as unique diastereoisomers. The scope of the process is illustrated by over sixty examples, including scaffolds present in natural alkaloids, and the mechanistic proposal is suppported by DFT-based computations.

Synthesis of two new enrichable and MS-cleavable cross-linkers to define protein-protein interactions by mass spectrometry

The cross-linking Mass Spectrometry (XL-MS) technique extracts structural information from protein complexes without requiring highly purified samples, crystallinity, or large amounts of material. However, there are challenges to applying the technique to protein complexes in vitro, and those challenges become more daunting with in vivo experiments. Issues include effective detection and identification of cross-linked peptides from complex mixtures. While MS-cleavable cross-linkers facilitate the sequencing and identification of cross-linked peptides, enrichable cross-linkers increase their detectability by allowing their separation from non-cross-linked peptides prior to MS analysis. Although a number of cross-linkers with single functionality have been developed in recent years, an ideal reagent would incorporate both capabilities for XL-MS studies. Therefore, two new cross-linkers have been designed and prepared that incorporate an azide (azide-A-DSBSO) or alkyne (alkyne-A-DSBSO) to enable affinity purification strategies based on click chemistry. The integration of an acid cleavage site next to the enrichment handle allows easy recovery of cross-linked products during affinity purification. In addition, these sulfoxide containing cross-linking reagents possess robust MS-cleavable bonds to facilitate fast and easy identification of cross-linked peptides using MS analysis. Optimized, gram-scale syntheses of these cross-linkers have been developed and the azide-A-DSBSO cross-linker has been evaluated with peptides and proteins to demonstrate its utility in XL-MS analysis.

A tandem reaction of 4-bromoalkyl aldehydes with sodium azide: Synthesis of 5,6,7,7a-tetrahydro-pyrrolo[1,2-d]-[1.2.3.4]oxatriazole

5,6,7,7a-Tetrahydro-pyrrolo[1,2-d]-[1.2.3.4]oxatriazoles were synthesized through a nucleophilic substitution-cycloaddition tandem reaction of 4-bromoalkyl aldehydes with sodium azide.

A novel solid-phase reductive alkylation route to acridine and dansyl polyamine conjugates

Solid-phase organic synthesis (SPOS) routes to target unsymmetrical polyamines and their acridinyl and dansyl conjugates have been developed based upon borane-pyridine complex (BAP) mediated reductive alkylation, azide reduction with triphenylphosphine, and the use of pent-4-enoyl (Pnt) as an orthogonal amine protecting group.

Structure - Immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 2. Structural modifications of the spermidine moiety

A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Various substitutions of the spermidine 'D' region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. Various positions of methylation were first investigated leading to the discovery of the monomethylated malonic derivative 56h in which the pro-R hydrogen of the methylene α to the primary amine of the spermidine moiety has been replaced by a methyl group. Synthesis of the similarly methylated analogue of the previously reported glycolic derivative LF 08-0299 afforded 60c which demonstrated a powerful activity at a dose as low as 0.3 mg/kg in the GVHD model and was much more potent than DSG in the demanding heart allotransplantation model in rats. The improvement of in vivo activity was supposed to be related to an increase of the metabolic stability of the methylated analogues compared to the parent molecules. Due to its very low active dose, compatible with a subcutaneous administration in humans, and its favorable pharmacological and toxicological profile, 60e was selected as a candidate for clinical evaluation.

ETUDE DE LA CHIMIOSELECTIVITE DE LA REACTION DES DICHLOROBORANES AVEC LES AZIDES FONCTIONNELS: UNE SYNTHESE EFFICACE D'AMINES SECONDAIRES FONCTIONNALISEES.

The reaction of cyclohexyldichloroborane, used as a model, with a wide variety of functionalized azides has been studied.It has been shown to be an efficient synthesis of secondary amines in terms of chemioselectivity, yields and wide applicability.

THE USE OF ω-IODOAZIDES AS PRIMARY PROTECTED ELECTROPHILIC REAGENTS. ALKYLATION OF SOME CARBANIONS DERIVED FROM ACTIVE METHYLENE COMPOUNDS AND N,N-DIMETHYLHYDRAZONES.

Some carbanions derived from active methylene compounds and N,N-dimethylhydrazones were alkylated in good yields with the ω-iodoazides 3, 4 and 13 used as primary amino protected electrophilic reagents.

La reaction d'ω-azidocetones avec la triphenylphosphine: une voie d'acces generale aux imines cycliques

The ω-azidoketones RC(=O)-CH(R')-(CH2)n-CH(R'')-N3 react with triphenylphosphine in anhydrous media to give 5, 6 and 7 membered cyclic imines via an intramolecular aza-Wittig reaction with good yields.A general synthesis of ω-haloketones which are the precursors of the azidoketones was also devised.