Derivatives of 2-azabicyclo2.2.1!heptane, their preparation and their application
AssigneeRhone-Poulenc Rorer S.A.
InventorsDenis Largeau, Patrick Leon
Life of this patent
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Abstract
Novel derivatives of 1R- or 1S-2-azabicyclo2.2.1!heptane with the general formula (I) or (I'), their preparation and their application. ##STR1## In the general formulas (I) and (I'), R represents a hydrogen atom or a group with the formula ##STR2## respectively, in which R.sub.1 represents an alkyl group containing 1-4 carbon atoms and Ar represents an optionally substituted phenyl or .alpha.- or .beta.-naphthyl group. The novel products with the general formula (I) are particularly useful for the preparation of adenosine agonists.
Claims9
A method for the preparation of a compound of formula ##STR13## wherein R represents a hydrogen atom, comprising hydrogenating a compound of formula ##STR14## wherein R represents respectively a group of formula ##STR15## wherein R.sub.1 represents an alkyl group containing 1-4 carbon atoms and Ar represents a phenyl or .alpha.- or .beta.-naphthyl group, optionally substituted by one or more atoms or groups, which may be identical or different, selected from halogen atoms and alkyl groups containing 1-4 carbon atoms, alkoxy groups containing 1 to 4 carbon atoms, or nitro groups, with hydrogen in the presence of a catalyst in an organic solvent selected from aliphatic alcohols containing 1-3 carbon atoms.
A method for the preparation of a compound of formula VIII ##STR16## wherein R'.sub.1 and R".sub.1, which are identical or different, represent an aliphatic organic acid group containing 2-4 carbon atoms or aromatic acid group, or R'.sub.1 and R".sub.1 taken together form a methylene group whose carbon atom is optionally substituted by one or more groups, which may be identical or different, selected from alkyl groups containing 1-4 carbon atoms, which can be taken together with the carbon atom to which the alkyl groups are attached to form an alicyclic group containing 5 or 6 carbon atoms, or phenyl groups, and G.sub.2 represents a hydrogen atom or a protecting group of an amino group, comprising:
- a) esterifying or acetalating a compound of formula I to protect the hydroxyl moieties thereof:
- ##STR17## wherein R represents a hydrogen atom or a group of formula II:
- ##STR18## wherein R.sub.1 represents an alkyl group containing 1-4 carbon atoms and Ar represents a phenyl or .alpha.- or .beta.-naphthyl group, optionally substituted by one or more atoms or groups, which may be identical or different, selected from halogen atoms and alkyl groups containing 1-4 carbon atoms, alkoxy groups containing 1 to 4 carbon atoms, or nitro groups, with hydrogen in the presence of a catalyst in an organic solvent selected from aliphatic alcohols containing 1-3 carbon atoms, to yield a compound of formula VI ##STR19## wherein R, R'.sub.1 and R".sub.1 are defined as above;
- b) transforming the compound of formula VI to a compound of formula VII:
- ##STR20## wherein R'.sub.1 and R".sub.1 are defined as above, and G.sub.2 represents a protecting group of the nitrogen atom, by either
- i) hydrogenating the compound of formula VI, in which R represents a group of formula II and protecting the nitrogen atom with a protecting group, wherein the hydrogenating and protecting are optionally conducted simultaneously, or
- ii) protecting the nitrogen atom on the compound of formula VI, wherein R represents a hydrogen atom, with a protecting group;
- and then
- c) oxidizing the compound of formula VII to the compound of formula VIII.
A method for the preparation of a compound of formula VIII ##STR21## wherein R'.sub.1 and R".sub.1, which are identical or different, represent an aliphatic organic acid group containing 2-4 carbon atoms or aromatic acid group, or R'.sub.1 and R".sub.1 taken together form a methylene group whose carbon atom is optionally substituted by one or more groups, which may be identical or different, selected from alkyl groups containing 1-4 carbon atoms, which can be taken together with the carbon atom to which the alkyl groups are attached to form an alicyclic group containing 5 or 6 carbon atoms, or phenyl groups, and G.sub.2 represents a hydrogen atom or a protecting group of an amino group, comprising oxidizing a compound of formula VI ##STR22## wherein R'.sub.1 and R".sub.1 are defined above and R represents a hydrogen atom, with RuO.sub.4, which is optionally generated in situ in the presence of an oxidant, to obtain a lactam compound, and then protecting the nitrogen of the lactam by reacting the lactam with di-t-butyl dicarbonate in an aliphatic alcohol containing 1-3 carbon atoms at between 0.degree. C. and 50.degree. C.
Dependencies are inferred from the claim text.