Patent EP-0110826-B1 (EP)
IPC: C07D499/00
Filed: 1983-11-10
Granted: 1987-08-19
Abstract: 1. Claims (for the Contracting States : BE, CH, LI, DE, FR, GB, IT, LU, NL, SE) 2-heterocyclyl-lower alkyl-6-hydroxy-lower alkyl-2-penem compounds of the formula  see diagramm : EP0110826,P37,F1  in which R1 represents hydrogen or methyl, R2 represents hydroxy or protected hydroxy, R3 represents carboxy or protected carboxy R'3 , especially esterified carboxy R'3 that can be cleaved under physiological conditions, R4 represents a monocyclic, optionally partially saturated 5-membered heteroaryl radical that has from 1 to 4 ring nitrogen atoms and is bonded via a tertiary ring nitrogen atom to the radical -(CH2 )m - or a corresponding partially saturated 6-membered heteroaryl radical having from 1 to 3 ring nitrogen atoms, these radicals being unsubstituted or substituted by hydroxy, lower alkoxy, lower alkanoyloxy, halogen, mercapto, lower alkylthio, phenylthio, lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, carboxy-lower alkyl, amino-lower alkyl, di-lower alkylamino-lower alkyl, sulpho-lower alkyl, amino, lower alkylamino, di-lower alkylamino, lower alkyleneamino, lower alkalnoylamino, carboxy, lower alkoxycarbonyl, optionally N-mono- or N,N-di-lower alkylated carbamoyl, cyano, sulpho, sulphamoyl, phenyl that is optionally substituted by lower alkyl, nitro, lower alkoxy and/or by halogen, cycloalkyl, nitro, oxo and/or oxido, the radicals designated "lower" containing up to 7 carbon atoms, and m represents an integer from 1 to 4, salts of compounds of the formula I that have a salt-forming group, optical isomers of compounds of the formula I and mixtures of these optical isomers. 1. Claims (for the Contracting State AT) Process for the manufacture of compounds of the formula  see diagramm : EP0110826,P40,F1  in which R1 represents hydrogen or methyl, R2 represents hydroxy or protected hydroxy, R3 represents carboxy or protected carboxy R'3 , especially esterified carboxy R'3 that can be cleaved under physiological conditions, R4 represents a mono-cyclic, optionally partially saturated 5-membered heteroaryl radical that has from 1 to 4 ring nitrogen atoms and is bonded via a tertiary ring nitrogen atom to the radical -(CH2 )m - or a corresponding partially saturated 6-membered heteroaryl radical having from 1 to 3 ring nitrogen atoms, these radicals being unsubstituted or substituted by hydroxy, lower alkoxy, lower alkanoyloxy, halogen, mercapto, lower alkylthio, phenylthio, lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, carboxy-lower alkyl, amino-lower alkyl, di-lower alkylamino-lower alkyl, sulpho-lower alkyl, amino, lower alkylamino, di-lower alkylamino, lower alkyleneamino, lower alkanoylamino, carboxy, lower alkoxycarbonyl, optionally N-mono- or N,N-di-lower alkylated carbamoyl, cyano, sulpho, sulphamoyl, phenyl that is optionally substituted by lower alkyl, nitro, lower alkoxy and/or by halogen, cycloalkyl, nitro, oxo and/or oxido, the radicals designated "lower" containing up to 7 carbon atoms, and m represents an integer form 1 to 4, their salts, their optical isomers and mixtures of their optical isomers, characterised in that a) an ylide compound of the formula  see diagramm : EP0110826,P40,F2  in which R1 , R2 , R'3 , R4 and m have the meanings given under formula I, a hydroxy group R2 and any functional groups which may additionally be present in the radical R4 preferably being in protected form, Z represents oxygen or sulphur and X (anion) represents either a trisubstituted phosphonio group or a diesterified phosphono group together with a cation, is cyclised, or b) a compound of the formula  see diagramm : EP0110826,P40,F3  in which R1 , R2 , R'3 , R4 and m have the meanings given under formula I, a hydroxy group R2 and any functional groups which may additionally be present in the radical R4 preferably being in protected form, is treated with an organic compound of trivalent phosphorus, or c) a compound of the formula  see diagramm : EP0110826,P40,F4  in which R1 , R2 , R'3 and m have the meanings given above, and Q represents a reactive esterified hydroxy group, is reacted with an agent that introduces the azaheterocyclyl radical R4 , and, if desired or necessary, in a resulting compound of the formula I a protected hydroxy group R2 is converted into a free hydroxy group, and/or, if desired, in a resulting compound of the formula I a protected carboxy group R'3 is converted into the free carboxy group R'3 , and/or, if desired, other protected functional groups present in the radical R4 are converted into the free functional groups, and/or, if desired, a resulting compound of the formula I a radical R4 is converted into a different radical R4 , and/or, if desired, a resulting compound having a salt-forming group is converted into a salt, or a resulting salt is converted into the free compound or into a different salt, and/or, if desired, a resulting mixture of isomeric compounds is separated into the individual isomers.