KP-736

Chemical Name: (6R,7R)-7-[2-(2-Aminothiazol-4-yl)-2(Z)-(1,5-dihydroxy-4-oxo-1,4-dihydropyridin-2-ylmethoxyimino)acetamido]-3-(1,2,3-thiadiazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid disodium salt; [6R-[6alpha,7beta(Z)]-7-[[(2-Amino-4-thiazolyl)[[(1,4-dihydro-1,5-dihydroxy-4-oxo-2-pyridinyl)methoxy]imino]acetyl]amino]-8-oxo-3-[(1,2,3-thiadiazol-5-ylthio)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium salt
CAS No. 114875-57-9 (free acid), 114830-63-6 (monoNa salt), 114875-68-2 (monotrifluoroacetate)
项目整合开发状态: Phase II
项目研究机构: Kaken (Originator)
合成路线:The alkylation of 5-hydroxy-2-(hydroxymethyl)-4-pyrone (I) with diphenyldiazomethane in ethanol gives 5-(diphenylmethoxy)-2-(hydroxymethyl)-4-pyrone (II),which is treated with hydroxylamine in hot ethanol - water to afford 5-(diphenylmethoxy)-1-hydroxy-2-(hydroxymethyl)-4-pyridone (III).The alkylation of (III) with diphenylmethyl chloride,K2CO3 and NaI in DMSO yields 1,5-bis(diphenylmethoxy)-2-(hydroxymethyl)-4-pyridone (IV),which is condensed with N-hydroxyphthalimide (V) by means of triphenylphosphine in THF to give 1,5-bis(diphenylmethoxy)-2-(phthalimidooxymethyl)-4-pyridone (VI).The reaction of (VI) with hydrazine in ethanol affords the corresponding aminooxy derivative (VII),which is condensed with 2-[2-(triphenylmethylamino)thiazol-4-yl]glyoxylic acid (VIII) in CHCl3 - ethanol to yield 2(Z)-[1,5-bis(diphenylmethoxy)-4-oxo-1,4-dihydropyridin-2-ylmethoxyimino]-2-[2-(triphenylmethylamino)thiazol-4-yl]acetic acid (IX).The condensation of (IX) with (6R,7R)-7-amino-3-(chloromethyl)-3-cephem-4-carboxylic acid 4-methoxybenzyl ester (X) by means of NaHCO3,1-hydroxybenzotriazole (HBT) and dicyclohexylcarbodiimide (DDC) in ethyl acetate - water gives the corresponding 7-acetamide derivative (XI),which by a new condensation with sodium 1,2,3-thiadiazole-5-thiolate (XII) in DMF - ethanol affords the fully protected final product (XIII).Finally,this compound is deprotected by a treatment with trifluoroacetic acid and anisole,the sodium salt being obtained by treatment with HaHCO3 in water.