Patent EP-0119955-A2 (EP)
Inventor: WATTHEY JEFFREY W H DR
IPC: C07D223/16
Filed: 1984-02-06
Abstract: 1. Claims for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE Compounds of the general formula  see diagramm : EP0119955,P34,F1  wherein R**1 represents 4-aminobutyl, R**2 and R**3 represent, independently of each other, hydroxy or lower alkoxy, and S represents the chirality, or salts thereof. 1. Claims for Contracting State : AT A process for the preparation of a 3-(5-aminopentyl)- amino-1-benzazepin-2-one-1-alkanoic acid of the general formula  see diagramm : EP0119955,P38,F1  wherein R**1 represents 4-aminobutyl, R**2 and R**3 represent, independently of each other, hydroxy or lower alkoxy, and S represents the chirality, or a salt thereof, characterised in that a) a compound of the formula see diagramm : EP0119955,P38,F2  as the S-enantiomer or mixture of stereoisomers containing said enantiomer, wherein R**3 has the meanings given above, is alkylated with a compound of the formula see diagramm : EP0119955,P38,F3  as the S-enantiomer or mixture of stereoisomers containing said enantiomer, wherein Z is a reactive esterified hydroxy group and R**1 and R**2 have the meanings given above, or with a compound of the formula R**1 -CO-COR**2 wherein R**1 and R**2 have the meanings given above, in the presence of a reducing agent, with the temporary protection of the amino group and/or of hydroxy groups that may be present in any one of the radicals R**1 , R**2 and R**3 , or b) a compound of the formula  see diagramm : EP0119955,P39,F1  or a mixture of stereoisomers containing said compound, wherein S, R**1 and R**2 have the meanings given above, is alkylated with a compound of the formula Z-CH2 COR**3 wherein Z is a reactive esterified hydroxy group and R**3 has the meanings given above, preferably with the temporary protection of the amino group and/or of hydroxy groups that may be present in any one of the reactants, or c) a compound of the formula  see diagramm : EP0119955,P39,F2  wherein Y is oxo, a reactive esterified or etherified hydroxy group Z together with hydrogen or two reactive esterified or etherified hydroxy groups Z, and R**3 has the meanings given above, is condensed with an amine of the formula  see diagramm : EP0119955,P39,F3  as the S-enantiomer or mixture of stereoisomers containing said enantiomer, wherein R**1 and R**2 have the meanings given above, with the proviso that when Y is oxo or two esterified or etherified hydroxy groups, the condensation is carried out in the presence of a reducing agent, or d) in a compound of the formula  see diagramm : EP0119955,P39,F4  or in a mixture of stereoisomers containing said compound, wherein S and R**1 have the meanings given above, one of the symbols R**0' and R**0" is cyano and the other is cyano or COR**2 or, as appropriate, COR**3 as defined above, the cyano group(s) is(are) subjected to solvolysis, or e) a compound of the formula  see diagramm : EP0119955,P40,F1  or a mixture of stereoisomers containing said compound, wherein S, R**1 , R**2 and R**3 have the meanings given above, or a reactive ester thereof, is cyclised, or f) one or two double bonds in a compound of the formula see diagramm : EP0119955,P40,F2  wherein said double bond(s) is(are) located between C3 and C4, C4 and C5 and/or in the side-chain between the nitrogen atom and an adjacent carbon atom, and wherein R**1 , R**2 and R**3 have the meanings given above, is(are) saturated by treatment with a reducing agent, or g) the monocyclic lactam in a compound of the formula  see diagramm : EP0119955,P40,F3  or in a mixture of stereoisomers containing said compound, wherein S and R**3 have the meanings given above, is ringopened to give a compound of formula I wherein R**2 and R**3 are hydroxy, or h) a compound of the formula  see diagramm : EP0119955,P40,F4  or a mixture of stereoisomers containing said compound, wherein X is oxo, protected oxo or two esterified or etherified hydroxy groups, or wherein X is hydroxy or esterified or etherified hydroxy together with a hydrogen atom, and wherein S, R**1 , R**2 and R**3 have the meanings given above, is hydrogenolysed or reduced, or i) a compound of the formula see diagramm : EP0119955,P41,F1  or a mixture of stereoisomers containing said compound, wherein R**4 is a group convertible into 2-aminoethyl, and R**2 and R**3 have the meanings given above, is converted into a compound of formula I, or j) a compound of the formula  see diagramm : EP0119955,P41,F2  or a mixture of isomers containing said compound, wherein R**5 or R**6 is a group convertible into COR**2 or COR**3 , respectively, and the other is COR**2 or COR**3 as appropriate, or wherein R**5 and R**6 are groups convertible into COR**2 and COR**3 , and wherein S has the meaning given above, is converted into a compound of the formula I, or k) in a compound of the formula  see diagramm : EP0119955,P41,F3  or in a mixture of stereoisomers containing said compound, wherein at least one of the groups Z**1 to Z**4 is a protective group, remaining groups Z**2 and Z**4 are hydrogen and remaining groups Z**1 and Z**3 are hydrogen or lower alkyl, with the proviso that at least one group of the remaining groups Z**1 and Z**3 is hydrogen, and wherein S has the meaning given above, in order to obtain a compound of formula I wherein one or both of the radicals R**2 and R**3 is(are) hydroxy, the protective group(s) is(are) removed and, if desired, a resulting compound of formula I is converted into another compound of formula I and/or, if desired, a resulting compound of formula I having salt-forming properties is converted into a salt thereof or a resulting salt is converted into another salt, or a free compound is liberated from such a salt, and/or, if desired, the optical isomer of formula I that has the S,S configuration with respect to the two centres of chirality is isolated from a mixture of stereoisomeric forms containing a compound of formula I.