Patent FR-2100681-B1 (FR)
IPC: C07D499/46
Filed: 1971-05-25
Granted: 1974-10-18
Abstract: 1301961 Preparation of ureido penicillins BAYER AG 25 May 1971 [25 May 1970 22 Aug 1970 1 Feb 1971 3 Feb 1971 9 March 1971] 16880/71 Heading C2A The invention comprises a process for the preparation of penicillins of Fomula (I) and salts thereof, which process comprises reacting a compound of Formula (52) or a condensation product of such a compound with a carbonyl compound, preferably acetone, of general formula (53) or a compound of general formula (54) or (55) at a temperature of -20‹ C. to +50‹ C. with a compound of general formula (57) or (58) or in a solvent and in the presence of a base when a compound of general fromula (52) or (53) is used, and in an anydrous solvent free of hydroxyl groups with or without the presence of a base when a compound of general formula (54) or (55) is used; and when a salt is derived converting the penicillin thus produced into the desired salt. In the above formulµ, A denotes a group of general formula wherein X is hydrogen or an alkyl, alkenyl, cycloalkyl or cycloalkenyl group with up to ten carbon atoms, or a vinyl, arylvinyl, mono-, di- or tri-haloalkyl, monoalkylamino, dialkylamino, monoarylamino or arylalkylamino group, or an alkoxy or aralkoxy group with up to eight carbon atoms, or a cycloalkoxy group with up to 7 carbon atoms, or an aryloxy group, or a group having one of the general formulae in which formulµ V is a divalent radical with one to three carbon atoms, n is 0, 1 or 2 and R 1 , R 2  and R 3 , which may be the same or different, each denote a hydrogen, chlorine, bromine, iodine or fluorine atom or a nitro, nitrile, dialkylamino, dialkylaminocarbonyl, alkanoylamino, alkoxycarbonyl, alkanoxyloxy, alkyl, alkoxy with up to 6 carbon atoms, sulphamyl or trifluoromethyl, Y is an alkyl, alkenyl, cycloalkyl or cycloalkenyl group with up to 10 carbon atoms, or a vinyl, propenyl, mono-, di- or trihalo alkyl group with up to 8 carbon atoms ; #Z- denotes a divalent group having one of the general formulµ in which n is an integer from 3 to 5 and the arrow of the divalent group Z means that the linkage of the two free valencies of the group #Z- with the nitrogen and carbon atoms of the group of general formula (3) is not arbitrary, but is orientated as indicated by the arrow; E denotes an oxygen or sulphur atom; and Q denotes a divalent radical ; particularly a radical having one of the general formulµ in which general formulµ G is a hydrogen atom or a C 1 -C 6  alkyl group, the arrow means that the linkage of the two free valencies of the group Q with the two nitrogen atoms of the group of Formula (4) is orientated as indicated by the arrow; and M is a group having one of the general formulµ In the above formulµ B denotes a phenyl group or a phenyl or thienyl group substituted by an alkyl, alkoxy or alkylthio group having 1 to 6 carbon atoms; and C* is a carbon atom which constitutes a chirality centre which can be in either of the two possible R- and S- configurations, R 4 , R 5  and R 6  are C 1 -C 6  alkyl groups and w is a halogen atom or an azide group. The invention also comprises D-α-(3- acetyl - 3 - methyl - ureido) - benzyl - penicillin, D - α - (3 - dimethylaminocarbonyl - 3 - methylureido) - benzylpenicillin, D - α - (pyrrolid - 2- on - 1 yl - carbonylamino) - benzylpencillin and D - α - (imidazolidin - 2 - on - 1 - yl - carbonylamino) benzylpenicillin and the sodium salts thereof. Phermaceutical compositions containing at least one of the above penicillins as antibiotically active ingredient have been prepared.