【结 构 式】 |
【分子编号】24087 【品名】benzhydryl 2-(2-amino-1,3-thiazol-4-yl)-2-[[2-(tert-butoxy)-2-oxoethoxy]imino]acetate 【CA登记号】 |
【 分 子 式 】C24H25N3O5S 【 分 子 量 】467.54572 【元素组成】C 61.65% H 5.39% N 8.99% O 17.11% S 6.86% |
合成路线1
该中间体在本合成路线中的序号:(VII)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.
【1】 Takaya, T.; Takasugi, H.; Yamanaka, H. (Fujisawa Pharmaceutical Co., Ltd.); Cephem compounds. EP 0071891; US 4515788; US 4649136; US 4736039 . |
【2】 Prous, J.; Castaner, J.; FK-089. Drugs Fut 1986, 11, 2, 103. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
23767 | Methoxybenzene; Methyl phenyl ether; Anisole | 100-66-3 | C7H8O | 详情 | 详情 | |
(A) | 23003 | Diphenyldiazomethane | C13H10N2 | 详情 | 详情 | |
(I) | 24081 | 2-[[2-(tert-butoxy)-2-oxoethoxy]imino]-2-(1,3-thiazol-4-yl)acetic acid | C11H14N2O5S | 详情 | 详情 | |
(II) | 24082 | 7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C7H8N2O3S | 详情 | 详情 | |
(III) | 24083 | 7-[[2-[[2-(tert-butoxy)-2-oxoethoxy]imino]-2-(1,3-thiazol-4-yl)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid | C18H20N4O7S2 | 详情 | 详情 | |
(IV) | 24084 | 2-[[2-(tert-butoxy)-2-oxoethoxy]imino]-2-[2-(formylamino)-1,3-thiazol-4-yl]acetic acid | C12H15N3O6S | 详情 | 详情 | |
(V) | 24085 | 2-(2-amino-1,3-thiazol-4-yl)-2-[[2-(tert-butoxy)-2-oxoethoxy]imino]acetic acid | C11H15N3O5S | 详情 | 详情 | |
(VI) | 24086 | benzhydryl 2-[[2-(tert-butoxy)-2-oxoethoxy]imino]-2-[2-(formylamino)-1,3-thiazol-4-yl]acetate | C25H25N3O6S | 详情 | 详情 | |
(VII) | 24087 | benzhydryl 2-(2-amino-1,3-thiazol-4-yl)-2-[[2-(tert-butoxy)-2-oxoethoxy]imino]acetate | C24H25N3O5S | 详情 | 详情 | |
(VIII) | 24088 | benzhydryl 2-[[2-(tert-butoxy)-2-oxoethoxy]imino]-2-(1,3-thiazol-4-yl)acetate | C24H24N2O5S | 详情 | 详情 | |
(IX) | 24089 | 2-oxo-2-(1,3-thiazol-4-yl)acetic acid | C5H3NO3S | 详情 | 详情 | |
(X) | 24090 | tert-butyl 2-(aminooxy)acetate | C6H13NO3 | 详情 | 详情 |