Patent ID: 6169180
Filing Date: 2001-01-02
Classification: C07D,Y02P

Abstract:
A process for the production of a 7-acylamino-3-(propen-1-yl)-3-cephem-4-carboxylic acid wherein the propen-1-yl group in position 3 of the ring structure is substituted in position 3' by a residue of a nucleophile, X, which process comprises: (a) reacting a compound of formula IX ##STR11## wherein R.sub.o is hydrogen or methoxy and R.sub.6 is a silyl protecting group which is trimethylsilyl, triethylsilyl, tri-n-propyl-silyl, tri-n-butylsilyl, methyldiethylsilyl, dimethylethylsilyl, phenyldimethylsilyl, tert-butyldiphenylsilyl, tert-butyldimethylsilyl or triphenylsilyl, with a reactant form of the nucleophile radical X to obtain a compound of formula IX wherein the iodine group is replaced by the residue of the nucleophile X, wherein the nucleophile radical X is (1) ##STR12## wherein Het.sub.1 is a 5- or 6-membered heterocycle which may contain one or two additional heteroatoms selected from oxygen, nitrogen or sulphur atoms, R.sub.7 is hydrogen, carboxy, carboxamido, a sulphonic acid radical, alkoxy, hydroxy, acyl, amino, alkylthio, mercapto, or both the R.sub.7 's are a saturated or unsaturated alkyl group, or form part of a saturated or unsaturated carbocyclic ring; (2) an aliphatic ammonium group of formula III ##STR13## wherein R.sub.2, R.sub.3 and R.sub.4 may be the same or different and are respectively alkyl, alkenyl, aryl, hydroxy lower alkyl, carbamoyl lower alkyl, amino lower alkyl, acylamino lower alkyl, cyano lower alkyl, carboxy lower alkyl or oxopropyl, or R.sub.2 with R.sub.3 and the nitrogen atom form a carbocyclic unsaturated ring which is alkyl-substituted by R.sub.4 in which R.sub.4 may additionally represent a 1,3- or 1,4-alkylene or vinylene bridge or R.sub.2 and R.sub.3 and the nitrogen atom form a carbocyclic saturated ring, wherein R.sub.4 is a vinylene bridge; (3) a saturated heterocyclic ammonium group which is 1-methylpyrrolidinium, pyrrolidinium, piperidinium, 1-methylpiperidinium, 1-methylpiperazinium, 1-methylpyrazolidinium, 1,5-diazabicyclo[3.3.0]octan-1-ium, 1,4-diazabicylo[2.2.2]octan-1-ium, quinuclidinium or 1-aza-5-methyl-4,6-dioxabicyclo[3.3.1]nonan-1-ium; (4) a nitrogen base of formula IV --NH--R.sub.5 IV wherein R.sub.5 is hydrogen or has the significance of R.sub.2 above; (5) a tetrazole, triazole, imidazole, pyrrolidine or pyrazole group; (6) a heterocyclic thio radical of formula V ##STR14## wherein Het.sub.2 is (i) 1,5-dihydroxy-4-pyridon-2-yl, (ii) 5-hydroxy-1-methyl-4-pyridon-2-yl, (iii) 5-hydroxy-4-pyridon-2-yl, (iv) 1-methyl-1H-tetrazol-5-yl, (v) 2-methyl-1,3-4-thiadiazol-5-yl, (vi) 1-carboxymethyl-1H-tetrazol-5-yl, (vii) 6-hydroxy-2-methyl-5-oxo-2H-1,2,4-triazin-3-yl, 1,2,3-triazol-5-yl, or (viii) 4-methylthiazol-5-yl; (7) a thio radical of formula VI --S--R.sub.8 VI in which R.sub.8 is alkyl, alkenyl, aryl, acyl, carbamoyl, thiocarbamoyl or carbalkoxy radical or a thio-analog thereof; or (8) N.sub.3 ; and which process further comprises (b) acylating the amine group in position 7 with an acylating agent.