Patent EP-0102929-B1 (EP)
IPC: C07D295/08
Filed: 1983-09-01
Granted: 1987-07-01
Abstract: For the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE 1. A compound of the general formula I  see diagramm : EP0102929,P33,F1  Wherein each of R1  and R2  independently of the other represents hydrogen or lower alkyl ; or R1  and R2 together with the adjacent nitrogen atom represent piperidino or pyrrolidino or a five- or six-membered saturated heterocyclic ring containing NH, N-lower alkyl, O or S ; R3  represents hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl ; Ar represents phenyl or phenyl substituted by one to three substituents selected from the group consisting of lower alkyl, lower alkoxy, lower alkenyloxy, lower alkynyloxy, lower alkylmercapto, lower alkylsulfinyl, lower alkylsulfonyl, halogen and trifluoromethyl, or by on lower alkylenedioxy ; and X represents O, S or N-lower alkyl ; and n represents an integer 1, 2 or 3 ; or an N-oxide thereof ; an acid addition salt thereof ; of an N-lower alkyl or N-benzyl quaternary salt thereof ; with the exception of the compound of formula I wherein R1  and R2 represent ethyl, R3  represents hydrogen, Ar represents phenyl, X represents O, and n is 3, or a salt thereof ; with the groups qualified by the term "lower" containing at most 7 carbon atoms. For the Contracting State : AT 1. A process for the preparation of a novel propylamine derivative of the general formula I  see diagramm : EP0102929,P37,F1  Wherein each of R1  and R2 independently of the other represents hydrogen or lower alkyl ; or R1 and R2 together with the adjacent nitrogen atom represent piperidono or pyrrodino or a five- or six-membered saturated heterocyclic ring containing NH, N-lower alkyl, O or S ; R3  represents hydrogen, lower alkyl, lower alkoxy, halogen or trifluoromethyl ; Ar represents phenyl or phenyl substituted by one to three substituents selected from the group consisting of lower alkyl, lower alkoxy, lower alkenyloxy, lower alkynyloxy, lower alkylmercapto, lower alkylsulfinyl, lower alkylsulfonyl, halogen and trifluoromethyl, or by on lower alkylenedioxy ; and X represents O, S or N-lower alkyl ; and n represents an integer 1, 2 or 3 ; or of an N-oxide thereof ; an acid addition salt thereof ; of an N-lower alkyl or N-benzyl quaternary salt thereof ; with the exception of the compound of formula I wherein R1  and R2 represent ethyl, R3 represents hydrogen, Ar represents phenyl, X represents O, and n is 3, or a salt thereof ; with the groups qualified by the term "lower" containing at most 7 carbon atoms ; which process comprises a) condensing a compound of the formula II  see diagramm : EP0102929,P37,F2  or an acid addition salt thereof, with a compound of the formula III AR-Y(III) wherein R1 , R2 , R3 , n and Ar are as defined above, one of the symbols W and Y represents a group XH or XH in a metal salt from, in which X is as defined above, and the other one represents the group XH in a reactive esterified form thereof or as an N,N'-disubstituted isourea or isothiourea derivative ; or b) alkylating an amine of the formula IV  see diagramm : EP0102929,P37,F3  or an acid addition salt thereof, with a compound of the formula V  see diagramm : EP0102929,P38,F4  in which Z is a hydrogen atom together with a reactive esterified hydroxyl group of the oxo group and Ar, X, R3 and n are as defined above, and if Z is the oxo group, said alkylation is carried out under reductive conditions ; or c) reducing a compound structurally analogous to a compound of formula I as defined above, wherein an oxo group is present on at least one carbon atom adjacent to the amino nitrogen ; or d) saturating with hydrogen a multiple bond or multiple bonds in a compound structurally analogous to the compound of formula I as defined above and wherein one or two double bonds are present in the aliphatic moiety of the molecule inclusive of the amino group ; or e) removing the radial R0 from a compound of the formula VI  see diagramm : EP0102929,P38,F5 wherein R2 , R3 , X, n and Ar are as defined above and R0  is an amino proctective group, to obtain a compound of formula in which R1 is hyrogen ; or f) reducing a compound of the formula VII  see diagramm : EP0102929,P38,F5  wherein T represents cyano or azidomethyl ; and R3 , X, n and Ar are as defined above to obtain a compound of formula I wherein R1  and R2  are hydrogen ; or g) condensing a compound of the formula VIIA  see diagramm : EP0102929,P39,F6  with a compound of the formula VIIB  see diagramm : EP0102929,P39,F6  wherein one of the groups Q and M represents a removable group, and the other represents a metal or halometal radical, and Ar, X, R1  to R3  and n are as defined above, if necesseray while temporarily protecting any interfering reactive group in all these processes, and isolating the resultant compound of formula ; and/or, if  required, converting a resultant compound of formula I into another compound of formula I, and/or, if require, converting a resultant free compound into a salt or a resultant salt into the free compound or into another salt, and/or, if required, resolving a mixture of isomers or racemates obtained into the single isomers or racemates, and/or, if required, resolving a racemate obtained into the optical antipodes.