合成路线:1) The protection of the amino group of 2-(2-aminothiazol-4-yl)-2(Z)-(hydroxyimino)acetic acid ethyl ester (I) with di-tert-butyl dicarbonate,dimethylaminopyridine and NaOH gives 2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(hydroxyimino)acetic acid (II),which is then treated with triphenylmethyl chloride (Tr-Cl) and K2CO3 in DMF to afford 2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(triphenylmethoxyimino)acetic acid (III).The condensation of (III) with 7beta-amino-3-(methanesulfonyloxy)-3-cephem-4-carboxylic acid diphenylmethyl ester (IV) by means of phenylphosphoryl dichloride and N-methylmorpholine gives the 7beta-acetamido derivative (V),which is then condensed with 4-(acetylsulfanylmethylsulfanyl)-1-(triphenylmethyl)-1,2,3-triazole (VI) by means of NaOMe in THF/DMF/methanol to yield the fully protected compound (IX).Finally,this compound is deprotected by a treatment with AlCl3 anisole.The triazole (VI) can be obtained by reaction of the sodium salt of 1,2,3-triazole-4-thiol (VII) with thioacetic acid S-(chloromethyl)ester (VIII) in DMS followed by NH-protection with triphenylmethyl chloride.
参考文献标题:Triazolylthiomethylthio cephalosporin hydrochloride,its crystalline hydrate and the production of the same
文献作者:Takahashi,H.; Ide,Y.(Shionogi & Co.Ltd.)
参考来源:EP 0581552; JP 1994092970; US 5407929
合成路线:1) The protection of the amino group of 2-(2-aminothiazol-4-yl)-2(Z)-(hydroxyimino)acetic acid ethyl ester (I) with di-tert-butyl dicarbonate,dimethylaminopyridine and NaOH gives 2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(hydroxyimino)acetic acid (II),which is then treated with triphenylmethyl chloride (Tr-Cl) and K2CO3 in DMF to afford 2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(triphenylmethoxyimino)acetic acid (III).The condensation of (III) with 7beta-amino-3-(methanesulfonyloxy)-3-cephem-4-carboxylic acid diphenylmethyl ester (IV) by means of phenylphosphoryl dichloride and N-methylmorpholine gives the 7beta-acetamido derivative (V),which is then condensed with 4-(acetylsulfanylmethylsulfanyl)-1-(triphenylmethyl)-1,2,3-triazole (VI) by means of NaOMe in THF/DMF/methanol to yield the fully protected compound (IX).Finally,this compound is deprotected by a treatment with AlCl3 anisole.The triazole (VI) can be obtained by reaction of the sodium salt of 1,2,3-triazole-4-thiol (VII) with thioacetic acid S-(chloromethyl)ester (VIII) in DMS followed by NH-protection with triphenylmethyl chloride.
参考文献标题:Orally active cephalosporins.II.Synthesis and structure-activity relationships of new 7beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-cephalosporins with 1,2,3-triazole in C-3 side chain
文献作者:Kume,M.; Kubota,T.; Kimura,Y.; Nakashimizu,H.; Motokawa,K.; Nakano,M.
参考来源:J Antibiot 1993,46(1),177-92
合成路线:1) The protection of the amino group of 2-(2-aminothiazol-4-yl)-2(Z)-(hydroxyimino)acetic acid ethyl ester (I) with di-tert-butyl dicarbonate,dimethylaminopyridine and NaOH gives 2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(hydroxyimino)acetic acid (II),which is then treated with triphenylmethyl chloride (Tr-Cl) and K2CO3 in DMF to afford 2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(triphenylmethoxyimino)acetic acid (III).The condensation of (III) with 7beta-amino-3-(methanesulfonyloxy)-3-cephem-4-carboxylic acid diphenylmethyl ester (IV) by means of phenylphosphoryl dichloride and N-methylmorpholine gives the 7beta-acetamido derivative (V),which is then condensed with 4-(acetylsulfanylmethylsulfanyl)-1-(triphenylmethyl)-1,2,3-triazole (VI) by means of NaOMe in THF/DMF/methanol to yield the fully protected compound (IX).Finally,this compound is deprotected by a treatment with AlCl3 anisole.The triazole (VI) can be obtained by reaction of the sodium salt of 1,2,3-triazole-4-thiol (VII) with thioacetic acid S-(chloromethyl)ester (VIII) in DMS followed by NH-protection with triphenylmethyl chloride.
合成路线:2) The condensation of 1,2,3-triazol-4-thiol (X) with bromochloromethane by means of NaH gives 4-(chloromethylsulfanyl)-1,2,3-triazole (XI) with is treated with NaI in hot acetone to afford 4-(iodomethylsulfanyl)-1,2,3-triazole (XII).The reaction of (XII) with the silver mercaptide of the 7beta-[2-[2-(tert-butoxycarbonylamino)thiazol-4-yl]-2(Z)-(triphenylmethoxyimino)acetamido]-3-sulfanyl-3-cephem-4-carboxylic acid diphenylmethyl ester 1beta-oxide (XIII) in HMPT yields the condensation product (XV),which is then treated with PCl3 in DMF to eliminate the 1beta-oxide oxygen,affording the protected compound (XVI),which is deprotected with AlCl3 in anisole,as before.
参考文献标题:S-1090
文献作者:Mealy,N.; Castar,J.
参考来源:Drugs Fut 1996,21(3),254
产品链接: CAS No. 154776-45-1›› 产品链接: CAS No.140128-74-1››