83213-66-5

Upstream product

• 909396-90-3 [(1S,2R)-2-(aminomethyl)-2-(4-methylphenyl)cyclopropyl]methanol 
• 66504-76-5 (1R,2S)-1-p-Tolyl-cyclopropane-1,2-dicarboxylic acid dimethyl ester 
• 77053-52-2 methyl bromo(4-methylphenyl)acetate 
• 66504-84-5 (1R,5S)-1-p-Tolyl-3-aza-bicyclo[3.1.0]hexane-2,4-dione 

Downstream Products

• 66504-82-3 (1R,5S)-1-(4-methylphenyl)-3-azabicyclo<3.1.0>hexane hydrochloride 

Relevant academic research and scientific papers

Chlorination/cyclodehydration of amino alcohols with SOCl2: An old reaction revisited

(Chemical Equation Presented) A simple, one-pot preparation of cyclic amines via efficient chlorination of amino alcohols with use of SOCl2 has been developed. This approach obviates the need for the classical N-protection/O-activation/cyclization/deprotection sequence commonly employed for this type of transformation. The reaction pathways and the general scope of this method have also been investigated.

METHODS AND COMPOSITIONS FOR PRODUCTION, FORMULATION AND USE OF 1-ARYL-3-AZABICYCLO[3.1.0] HEXANES

The invention provides novel l-aryl-3-azabicyclo[3.1.0] hexanes that are active for modulating biogenic amine transport, along with compositions and methods for using these compounds to treat central nervous system disorders. Certain l-aryl-3-azabicyclo[3.1.0] hexanes are provided that have at least one substituent on the aryl ring. In other embodiments l-aryl-3-azabicyclo[3.1.0] hexanes are provided that have a substitution on the nitrogen at the '3' position. In additional embodiments l-aryl-3-azabicyclo[3.1.0] hexanes are provided which have one substitution on the aryl ring, as well as a substitution on the nitrogen at the '3' position. The invention also provides novel methods of making aryl- and aza-substituted l-aryl-3-azabicyclo[3.1.0] hexanes, including synthetic methods that form novel intermediate compounds of the invention for producing aryl- and aza-substituted l-aryl-3-azabicyclo[3.1.0] hexanes.

Stereocontrolled synthesis of trisubstituted cyclopropanes: Expedient, atom-economical, asymmetric syntheses of (+)-bicifadine and DOV21947

An expedient, atom-economical, asymmetric synthesis of 1-aryl-3- azabicyclo[3.1.0]hexanes, including (+)-Bicifadine and DOV21947, in a single-stage through process without isolation of any intermediates has been developed. The key of this synthesis is the in-depth mechanistic understanding of the complicated epoxy nitrile coupling at each reaction stage. Therefore, the desired trisubstituted cyclopropane can be prepared in high ee and yield by controlling the reaction pathway through manipulating the nitrile anion aggregation state.

1-Aryl-3-azabicyclohexanes, a New Series of Nonnarcotic Analgesic Agents

A series of 1-aryl-3-azabicyclohexanes was synthesized by hydride reduction of 1-arylcyclopropanedicarboximides.Hydroxyphenyl analogues 20, 22, and 24 were prepared by EtSNa-DMF ether cleavage of the corresponding methoxyphenyl analogues 2m, 2n, and 23, respectively, with the secondary amines 20 and 22 going through the N-formyl intermediates 19 and 21.The p-ethoxy analogue 26 was obtained by O-ethylation of 19, followed by base hydrolysis of the amide 25.The greatest analgesic potency in mouse writhing and rat paw-pain assays was observed for para-substituted compounds.Bicifadine, 1-(4-methylphenyl)-3-azabicyclohexane (2b), was the most potent member of the series and is presently undergoing clinical trials in man.Analgesic activity of 2b is limited to the (+) enantiomer 2v, which has the 1R,5S absolute configuration as determined by single-crystal X-ray analysis.The N-methyl analogue (27d) of 2b showed significant analgesic potency, whereas the N-allyl (27a), N-(cyclopropylmethyl) (27b), and N-(n-hexyl) (27c) analogues were inactive.Bicifadine (2b) showed a nonnarcotic profile different from analogous azabicycloalkane and 3-phenylpyrrolidine analgesics.