Patent GB-1468349-A (GB)
Title: 10-bornanamine and 7,7-dimethyl-norbornan-1-amine and derivatives thereof
IPC: C07D209/44
Filed: 1973-03-06
Abstract: 1468349 10-Bornanamine and 7,7-dimethylnorbornan - 1 - amine and derivatives thereof GLAXO LABORATORIES Ltd 6 March 1974 [6 March 1973] 10894/73 Heading C2C [Also in Division A5] Novel 7,7 - dimethyl - [2,2,1] - bicycloheptanes having at the 1-position a group R and the physiologically acceptable salts thereof, wherein R is an amino- or aminomethyl group having a basic nitrogen atom and is substituted at the amino nitrogen atom (via a single or double bond) and/or at the 10-carbon atom by one or more aliphatic, cycloaliphatic, araliphatic, phenyl or substituted phenyl groups or, in the case of the amino group, by a heterocyclic group in which the nitrogen atom of the amino group forms part of the heterocyclic ring, or, in the case of N-substituted aminomethyl, by an oxo group at the 10-carbon atom, may be prepared (a) when the group R has a methylene group in an α-position in relation to the 1 or 10-nitrogen atom, by reducing the corresponding amide, (b) when R is a methylamino group, by reducing an ester of the coresponding carboxyamino compound, (c) when R is as in (b), reductively methylating the corresponding primary amine, (d) when R is an aliphatic or araliphatic imino or iminomethyl in which the methyl is optionally substituted by condensing the corresponding primary amine with an aldehyde or ketone, (e) when said compound is 1,3,5-tris-(bornan-10- yl)-1,3,5-hexahydrotriazine by reacting 10- bornanamine with formaldehyde, (f) when R is an aminomethyl group in which one of the hydrogen atoms on the methyl carbon atom is substituted by reducing the corresponding ketoxime, (g) when the 1 or 10-nitrogen atoms of R bears a phenyl or substituted phenyl substituent, by reacting the corresponding amine with a benzyne, (h) when the 1- or 10-nitrogen atoms of R is mono- or di-substituted by an aliphatic, cycloaliphatic or araliphatic group, by reacting the corresponding primary or secondary amine with a compound R<SP>5</SP>X where R<SP>5</SP> is an aliphatic, cycloaliphatic or araliphatic group and X is a readily eliminatable group, (i) when the 1- or 10-nitrogen of R forms part of a hydroxy-substituted heterocyclic ring which contains at least 3 carbon atoms, by cyclising a compound of the invention in which the nitrogen atom of R is substituted by a hydroxyalkyl group carrying a readily eliminatable group, there being at least 3 carbon atoms between the nitrogen and the amino group and the readily eliminatable group, (j) when R is aminomethyl in which the methyl group is substituted, by reducing the corresponding substituted nitromethyl compound, (k) when the 1-or 10-nitrogen atom of R is substituted by an aminoacyl group (the amino group of which is unsubstituted or substituted by one or two alkyl groups), by reacting the corresponding haloacyl compound with ammonia or mono- or dialkyl-amine, (d) when the 1- or 10-nitrogen atom of R forms part of a heterocyclic ring, by reacting the corresponding unsubstituted amine with a compound XR<SP>7</SP>X where X is a readily eliminatable group and R<SP>7</SP> is a divalent alkylene group (which may be interrupted by O or S) or a cyclic group bearing two mono-valent alkylene groups; or (m) when the 1- or 10-nitrogen of R is substituted by an aliphatic or araliphatic group, by reducing the compound in which the said nitrogen atom is linked to said group by a double bond. The various amide intermediates used as starting materials in process (a) are prepared by reaction of the corresponding acid chloride and amine. Similarly 10-bromoacetamido-bornane and 1 - bromoacetamido - 7,7 - dimethyl norbornane are prepared by reacting 10-Bornanamine or 1- amino - 7,7 - dimethyl - norbornane with bromoacetylbromide. 7,7 - Dimethylnorbornyl - 1 - methyl ketone oxime is prepared by reacting 7,7-dimethyl norbornane-1-carboxylic acid with methyl lithium to form 7,7-dimethylnorbornyl-1-methyl ketone followed by reaction with hydroxylamine hydrochloride.