139346-23-9

Basic information

• Product Name: 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane
• Synonyms: 1-Azabicyclo(2.2.1)heptane, 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-, exo-; 3-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo(2.2.1)heptane
• CAS NO: 139346-23-9
• Molecular Formula: C₁₁H₁₅N₃O
• Molecular Weight: 205.2563
• Mol File: 139346-23-9.mol

Chemical Properties

• Boiling Point: 344.9°C at 760 mmHg
• Flash Point: 162.4°C
• Density: 1.3g/cm³
• Vapor Pressure: 6.38E-05mmHg at 25°C
• Refractive Index: 1.604
• CAS DataBase Reference: 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane(139346-23-9)
• EPA Substance Registry System: 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane(139346-23-9)

Safety Data

• Hazardous Substances Data: 139346-23-9(Hazardous Substances Data)

Upstream product

• 51285-13-3 cyclopropanecarboxamide oxime 
• 133963-77-6 exo-(3R,4R)-methyl 1-azabicyclo<2.2.1>heptane-3-carboxylate 
• 133444-97-0 ethyl (3S,4R)-1-azabicyclo<2.2.1>heptane-3-carboxylate 

Relevant articles and documents

Enantiospecific Synthesis of the (4R)-1-Azabicycloheptane Ring System

An enantioselective synthesis of (4R)-1-azabicycloheptane derivatives is described commencing from readily available trans-4-hydroxy-L-proline which is converted into the key intermediate (3R)-N-(tert-butoxycarbonyl)-3-methylsulfonyloxypyrrolidine 4.Reaction of the sulfonate ester 4 with an enolate anion yields a mixtute of (3R)-pyrrolidineacetic esters 8 and 9 which are reduced to the corresponding alcohols 10 and 11.Conversion of the alcohols into the sulfonate esters 12 and 13 followed by deprotection of the pyrrolidine nitrogen leads to cyclisation yielding the (4R)-1-azabicycloheptane derivatives 14 and 15.

Synthesis, Physicochemical and Conformational Properties of (3R,4R)-3-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicycloheptane, a Novel M1 Selective Muscarinic Partial Agonist

The cyclopropyloxadiazole derivative described in the title has been shown to be a functionally selective M1 partial agonist with antagonist properties in M2 and M3 muscarinic receptor assays; conformational studies indicate free rotation around the oxadiazole-azanorbornane bond, whilst X-ray studies reveal that the cyclopropyl group is in conjugation with the oxadiazole C=N bond.

Substituted oxadiazoles and thiadiazoles for use in the treatment of glaucoma

The use of compounds for formula (I): STR1 or a salt or prodrug thereof; wherein one of X, Y, or Z is an oxygen or sulphur atom and the other two are nitrogen atoms, and the dotted circle represents two double bonds thus forming a 1,3,4-oxadiazole, 1,2,4-oxadiazole, 1,3,4-thiadiazole or 1,2,4-thiadiazole nucleus; R1 represents a non-aromatic azacyclic or azabicyclic ring system selected from STR2 wherein the broken line represents an optional chemical bond; the substituents R3 and R4 may be present at any position, including the point of attachment to the oxa- or thia-diazole ring, and independently represent hydrogen, C1-4 alkyl, halo, C1-4 alkoxy, hydroxy or carboxy, or R3 and R4 together represent carbonyl; the group R5 represents hydrogen or C1-4 alkyl; and R2 represents hydrogen, C1-8 hydrogen, C1-8 alkyl optionally substituted by hydroxy or fluoro, C2-8 alkenyl, OR7, SR7, NR7 R8, CN, CO2 R7, CONR7 R8 OR NHCONHR9 where R9 is C1-4 alkyl; wherein R7 and R8 independently represent hydrogen or saturated or unsaturated C1-4 alkyl provided that, when R7 and R8 in NR7 R8 are both hydrogen, at least one of R3 and R4 is C1-4 alkyl, in the treatment of glaucoma, novel compounds having such use, formulations containing them and their synthesis.

Oxadiazole and its salts, their use in treating dementia

The compound (3R, 4R)-3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane and its salts behave as a functionally selective muscarinic agonist and are useful in the treatment of neurological and mental disorders, preferably in a pharmaceutical formulation comprising the active compound in association with a pharmaceutically acceptable carrier. The compound can be prepared by methods analogous to those known in the art via suitable chiral intermediates and cyclopropyl carboxamide oxime.

ENANTIOSELECTIVE SYNTHESIS OF 3-SUBSTITUTED 1-AZABICYCLO(2.2.1)HEPTANES

A process for preparing a substantially pure enantiomer of a compound formula (I) STR1 wherein X is O or S; andR. sup.2 represents hydrogen,--CF 3,--OR 7,--SR 7,--NR 7 R 8,--CN,--COOR 7,--CONR 7 R 8, or a saturated or unsaturated, substituted or unsubstituted hydrocarbon group, wherein R. sup.7 and R. sup.8 are independently selected from hydrogen and C 1-2 alkyl provided that--NR 7 R 8 is other than NH 2 ; which process comprises cyclization of a compound of formula (10) or salt thereof: STR2 wherein X and R 2 are as defined in formula (I); and R 4 is a labile leaving group and optionally epimerizing the endo-diastereomer so prepared to produce the corresponding exo-diastereomer.

Lipophilic oxadiazoles

Oxadiazoles of formula I wherein one of X, Y and Z is an oxygen atom and the other two are nitrogen atoms, and the dotted circle represents aromaticity (two double bonds) thus forming a 1,3,4-oxadiazole or 1,2,4-oxadiazole nucleus; R1 represents a non-aromatic azacyclic or azabicyclic ring system; and R2 represents an optionally substituted saturated hyrocarbon group having at least three carbon atoms, or unsaturated hydrocarbon group having at least 6 carbon atoms, have particularly advantageous selective properties for use in the treatment and/or prevention of neurodegenerative diseases.