Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-06-25
1995-10-17
Robinson, Allen J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514469, 514422, 514403, 514305, 514306, 514320, 549462, 549467, 549469, 546135, 546138, 546196, 548557, 5483644, A61K 3134, A61K 3140, C07D30778, C07D20708
Patent
active
054591619
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP91/02512, filed Dec. 27, 1991.
The present invention relates to a new process for the preparation of substituted benzofuran derivatives.
An object of the invention is a new process for the preparation of compounds of formula (I) ##STR5## wherein one of R.sub.1 and R.sub.2 is hydrogen or halogen and the other is, independently, an amino group or a C.sub.2 -C.sub.4 alkanoyl amino group; R.sub.3 is hydrogen; a linear or branched C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or C.sub.2 -C.sub.4 alkoxycarbonyl group; halogen; or phenyl unsubstituted or substituted by a C.sub.1 -C.sub.4 alkyl group; A is a group --(CH.sub.2).sub.n -Het wherein Het is an optionally substituted heteromonocyclic or heterobicyclic ring containing one or two nitrogen atoms, and n is zero or an integer of 1 to 3; and the symbol .... represents a single or double bond. Also the salts and all the possible isomers of the compounds of formula (I) can be obtained by the new process of the invention. In the above formula (I) when one of R.sub.1 and R.sub.2 is a C.sub.2 -C.sub.4 alkanoyl amino, it is, preferably, acetylamino or propanoylamino, in particular acetylamino. Preferably R.sub.1 is amino and R.sub.2 is halogen, in particular chlorine or fluorine, more particularly a chlorine. When R.sub.3 is C.sub.1 -C.sub.4 alkyl, it is, preferably, methyl or ethyl; when R.sub.3 is C.sub.1 -C.sub.4 alkoxy, it is, preferably, methoxy or ethoxy; when R.sub.3 is C.sub.2 -C.sub.4 alkoxycarbonyl, it is, preferably methoxycarbonyl; when R.sub.3 is halogen, it is, preferably, chlorine; when R.sub.3 is phenyl substituted by C.sub.1 -C.sub.4 alkyl, it is preferably 4-methylphenyl. R.sub.3 is preferably hydrogen. The Het moiety of the substituent A is, preferably, containing one or two nitrogen atoms, either unsubstituted or substituted by one or more C.sub.1 -C.sub.4 alkyl groups, or by a benzyl group; or atom, wherein each of the condensed monocyclic ring, being the same or different, is a pentatomic or hexatomic monocyclic ring, said heterobicyclic ring being unsubstituted or substituted by one or more C.sub.1 -C.sub.4 alkyl groups, or by a benzyl group.
Preferably n is 0 or 1. Preferably the symbol .... represents a single bond. When the Het moiety of the substituent A is a heteromonocyclic ring of the above class i), it is preferably a pyrrole or pyrazole ring, preferably saturated, optionally substituted on the nitrogen atoms; more preferably, when Het is a saturated pyrrole ring, it is, in particular, a pyrrolidine unsubstituted or substituted at the nitrogen atom by C.sub.1 -C.sub.4 alkyl or benzyl; when Het is a saturated pyrazole ring, it is, in particular, a pyrazolidine substituted at the two nitrogen atoms by C.sub.1 -C.sub.4 alkyl. When the Het moiety of the substituent A is a heterobicyclic ring of the above class ii), it is, preferably, a saturated azaheterobicyclic ring containing one nitrogen atom optionally substituted by C.sub.1 -C.sub.4 alkyl or benzyl.
Specific examples of the substituent A meanings are: ##STR6## wherein m is zero or 1 and R' is hydrogen or methyl, and
With reference to the azabicyclic structures in the present specification, e.g. those reported hereabove, the symbol means that the azabicyclic ring may be either in the .alpha. (endo) or in the .beta. (exo) orientation. Consequently, anywhere a formula has a substituent with a symbol , the formula may represent a compound having the azabicyclic ring only in the .alpha.(endo) orientation or only in the .beta.(exo) orientation or the formula may represent a mixture of both compounds having the azabicyclic ring in the .alpha.(endo) orientation and compounds having azabicyclic ring in the .beta.(exo) orientation.
In particular when A in the compounds of formula (I) represents an azabicyclic ring having the structure reported above under e), f) g) or h), preferably the azabicyclic ring is in the .alpha. (endo) orientation.
Furthermore, when a chiral center is present, both individual optical isomers and their mixtures, e.g. racemates, are
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Bedeschi Angelo
Cabri Walter
Candiani Ilaria
De Bernardinis Silvia
Marchi Marcello
Farmitalia Carlo Erba S.r.l.
Lambkin Deborah
Robinson Allen J.
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