Document Type and Number:
Japanese Patent JPS5127679
Kind Code:
B1
Abstract:
1,241,657. Preparing 3-substituted-methyl cephalosporins. GLAXO LABORATORIES Ltd. 6 Aug., 1968 [21 Aug., 1967], No. 38494/67. Heading C2A. Cephalosporin analogues having a group or atom derived from a nucleophile on the exocyclic carbon atom at the 3-position are prepared by reacting a 7-amino- or 7#-acylaminocephalosporanic acid (or derivative thereof), having a group -CH 2 X at the 3-position, with a nucleophile to effect nucleophilic displacement of the group X by a group or atom derived from the nucleophile, the group X being the residue of an acid HX which acid has a pKa of not more than 4 and in which acid the group X does not contain a sulphur atom linked to the hydrogen atom H. Cephalosporanic acid derivatives used as starting materials may be the salts, esters or anhydrides. Such esters include those with carboxyl-protecting groups such as diphenylmethyl; #,#,#-trichloroethyl and tert.-butyl radicals. The group -CH 2 X may be halomethyl (e.g. chloro-, bromo- or iodomethyl), or an ester group -CH 2 -O-A wherein the esterifying group A is derived from formic acid, a haloacetic acid, a methoxy-, alkylthio- or cyano-acetic acid, glyoxylic acid, phenylpropiolic acid, a hemi-ester of malonic or oxalic acid, or phenylglyoxylic acid substituted in the ring with halogen, methyl or methoxy; or the group X may be isocyanato. Numerous nucleophiles are mentioned, including trialkylamines, pyridines, nitrogen heterocyclic amines containing other heteroatoms, cyanides, pyrroles, indoles, acetylenes, acetoacetic and malonic esters, cyclohexane-1,3-diones, thiourea, substituted thioureas, thioamides, thiosulphates, alkanols, phenols and water. The reaction is suitably effected in a polar medium (which may be the nucleophile itself) at pH 5-8 and between 0 and 120 C. Novel cephalosporins of formula wherein each of the groups B is a C 1 -C 6 alky1 group, or the groups B together with the adjacent N atom form a thiazole ring which may be substituted, are prepared by the aforesaid process.
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Application Number:
JP2762971A
Publication Date:
August 13, 1976
Filing Date:
April 28, 1971
Export Citation:
International Classes:
A61K31/545; C07D501/04; C07D501/24; C07D501/26; C07D501/38; E05D15/10; (IPC1-7): C07D501/24; C07D501/04