FK-089

(6R,7R)-7-[[(2Z)-2-(羧甲氧基亚基)-2-(1,3-噻唑-4-基)乙酰]氨基]-8-氧基-5-硫-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸Chemical Name: (6R,7R)-7-[(Z)-2-(4-Thiazolyl)-2-(carboxymethoxyimino)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0] oct-2-ene-2-carboxylic acid
CAS No. 86070-74-8
项目整合开发状态: Phase I
项目研究机构: Fujisawa (Originator)
合成路线:The condensation of 2-(tert-butoxycarbonylmethoxyimino)-2-(4 thiazolyl)acetic acid (I) with 7-amino 3-cephem-4-carboxylic acid (II) by means of the Vusmejer reagent (POCl3 and dimethylformamide) in ethyl acetate gives 7-[2-(tert-butoxycarbonylmethoxyimino)-2-(4-thiazolyl)acetamido]-3-cephem-4-carboxylic acid (III),which is then de protected with trifluoroacetic acid and anisole in methylene chloride.The starting acetic acid derivative (I) can be obtained by several different ways:1) The partial hydrolysis of 2-(tert-butoxycarbonylmethoxyimino)-2-(2-formamidothiazol-4yl) acetic acid (IV) with concentrated HCl in methanol gives 2-(tert-butoxycarbonylmethoxyimino)-2-(2-aminothiazol-4-yl)acetic acid (V),which is then deaminated with tert butyl nitrite in refluxing THF.2) The preceding deamination of (IV) can be performed in a similar way with previous esterification with diphenyldiazomethane,through compounds (VI),(VII) and (VIII).Compound (VIII) is submitted to a partial hydrolysis with trifluoroacetic acid.3) Compound (I) can also be obtained by condensation of 2-(4-thiazolylglyoxylic acid (IX) with tert-butyl-2-(aminooxy)acetate (X) by means of NaHCO3 in ethyl acetate.