Substituted azabicycloheptane derivatives, their preparation and

Details Substituted azabicycloheptane derivatives, their preparation and Substituted azabicycloheptane derivatives, their preparation and

1994-12-12

1995-12-05

McKane, Joseph K.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

548466, 546272, C07D20902, C07D40104

Patent

active

054730805

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to novel azabicycloheptane derivatives, their preparation and use for preparing pharmaceutical agents.
The invention relates to 3-azabicyclo[3.2.0]heptane derivatives of the formula I ##STR2## where R.sup.1 is phenyl, pyridyl, thienyl or pyrrolyl which is unsubstituted or mono-or disubstituted by halogen atoms, C.sub.1 -C.sub.4 -alkyl, trifluoromethyl, C.sub.1 -C.sub.4 -alkoxy, hydroxyl, amino, monomethylamino, dimethylamino, cyano or nitro groups, and fluorine, methoxy, hydroxyl or amino.
Preferred compounds of the formula I are those where R.sup.2 is hydrogen and R.sup.1 is phenyl which is unsubstituted or substituted by fluorine, chlorine, hydroxyl, methoxy or amino. The phenyl is preferably in the exo configuration.
The compounds of the formula I may also be in the form of salts.
The novel compounds can be prepared by subjecting an amine of the formula II ##STR3## where R.sup.1 and R.sup.2 have the abovementioned meanings, and R.sup.3 is hydrogen, acetyl, trifluoroacetyl or benzyl, to a photochemical 2+2 cycloaddition and eliminating any acyl or benzyl group R.sup.3.
The photoreaction takes place well in an inert solvent, preferably acetone, at from 20.degree. to 80.degree. C. A particularly suitable light source is a high-pressure mercury lamp. It may be advantageous to carry out the photocycloaddition in a quartz apparatus under a nitrogen atmosphere with or without the addition of about 1 mole of hydrochloric acid per mole of amine.
X-ray structural analysis shows that the photocycloaddition in most cases takes place highly diastereoselectively to give the bicyclic compounds I with the exo configuration in respect of R.sup.1 and R.sup.2 : ##STR4##
The two enantiomers can be isolated pure by racemate resolution, eg. using optically active tartaric acid derivatives.
The amines of the formula II are disclosed in the literature or can be prepared by either reacting an aldehyde R.sup.1 --CHO with vinylmagnesium chloride to give the allyl alcohol III ##STR5## subsequently rearranging with hydrogen chloride to the allyl chloride IV ##STR6## and finally substituting with the appropriate allylamine V ##STR7## or subjecting a cinnamaldehyde VI ##STR8## directly to reductive amination with the allylamine V.
The elimination of an acyl radical from the compounds II is expediently carried out by conventional methods of hydrolysis, Similar is true of the elimination of the benzyl radical.
The compounds of the formula I according to the invention are valuable intermediates in the synthesis of novel pharmacologically active compounds of the formulae VII and VIII ##STR9## where R.sup.1 and R.sup.2 have the stated meanings, ##STR10## (where R.sup.5 is hydrogen, hydroxyl or phenyl which is unsubstituted or substituted by a fluorine, chlorine or bromine atom, -C.sub.4 -alkyl or methoxy, -alkoxy, or together with the adjacent carbon atom is a C.dbd.O or C.dbd.S group, groups or nitrogen atoms, which a hydrogen in atom can be replaced by a hydroxyl, amino or C.sub.1 -C.sub.4 -alkoxy group or a halogen atom, and di-C.sub.1 -C.sub.4 -alkylamino, C.sub.1 -C.sub.4 -alkylthio or C.sub.1 -C.sub.4 -alkoxy, or together with the adjacent carbon atom is a C.dbd.O group, or is a C.sub.3 -C.sub.4 -alkylene group which is linked to Y and which may contain one or two non-cumulative double bonds and in which one CH or CH.sub.2 group can be replaced by a nitrogen or sulfur atom or an NH or N-CH.sub.3 group, and where the ring can be monosubstituted either by a fluorine or chlorine atom or a methyl, methoxy, nitro or amino group, or in the case of a benzene ring the latter can be mono-, di- or trisubstituted by fluorine or chlorine atoms or methyl, trifluoromethyl, nitro, hydroxyl, methoxy, amino, monomethyl- or dimethylamino groups, a C.sub.1 -C.sub.4 -alkyl, allyl or benzyl group on nitrogen atom No. 1 and may contain 1 to 3 non-cumulative double bonds, and their salts with physiologically tolerated acids.
The compounds of the formulae VII and VIII are obtained from the compounds I by reacting with compound

REFERENCES:
CA85:159806. Stereoselective . . . olefins. Oppolzer et al., 1976.
Helvetica Chimica ACTA, Bd. 59, Nr. 4, 1976, Oppolzer et 1. Stereoselective syntheses of benz(f) . . . Olefins.

Affiliated with

Also associated with

Rating

Substituted azabicycloheptane derivatives, their preparation and does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Substituted azabicycloheptane derivatives, their preparation and, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Substituted azabicycloheptane derivatives, their preparation and will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1375148