• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】34289

【品名】[(3aR,4R,6aR)-6-isocyanato-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl 4-nitrobenzoate

【CA登记号】

【 分 子 式 】C16H16N2O8

【 分 子 量 】364.31172

【元素组成】C 52.75% H 4.43% N 7.69% O 35.13%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IV)

The synthesis of RFCNU from 2,3-O-isopropylidene-5-O-p-nitrobenzoyl-beta-D-ribosyl bromide (III) has been described, as well as the preparation of 2,3-O-isopropylidene-5-O-p-nitrobenzoyl-beta-D-ribosyl bromide from 2,3-O-isopropylidene-D-ribosyl-furanose (I). Briefly, the synthesis is as follows: A cold solution of 2,3-O-isopropylidene-D-ribofuranose (I) in dry pyridine is stirred and treated with p-nitrobenzoyl chloride (A). Workup gives 2,3-O-isopropylene-1,5-di-O-p-nitrobenzoyl-D-ribofuranose (II), which is crystallized from methylene chloride/ether. (II) is added in portions to a dry solution of methylene chloride saturated with HBr at 0 C and stirred for 0.5 h. It is warmed to room temperature, the precipitated p-nitrobenzoic acid removed by filtration (under argon) and the filtrate concentrated. Addition of petroleum ether/diethyl ether and partial concentration by vacuum gives crystals of 2,3-isopropylidene-5-O-p-nitrobenzoyl-beta-ribosyl bromide (III). (III), dissolved in toluene, is reacted with silver isocyanate and refluxed under nitrogen. Silver bromide is filtered off and the filtrate concentrated by evaporation, yielding an oil. Dissolution of the oil in acetonitrile and cooling to -40 C yields crystals of isocyanato-1-O-isopropylidene-2,3-O-p-nitrobenzoyl-5-D-ribofuranose (IV). (IV) is reacted with an aqueous solution of 2-chloroethylamine (B) and the solution extracted with benzene. The organic base is separated, dried and refrigerated. Warming gives a yellow oil, which is treated with ethanol to give crystalline (chloro-2-ethyl)-1-(ribofuranosylisopropylidene-2',3'-p-nitrobenzoate-5')-3-urea (V). (V) is dissolved in methylene chloride, cooled to -40 C and an excess of liquid nitrosyl chloride (NOCl) is added with stirring. Addition of a mixture of chloroform and petroleum ether gives crystals of (chloro-2-ethyl)-1-(ribofuranosylisopropylidene-2',3'-p-nitrobenzoate-5')-3-nitrosourea (RFCNU). The synthesis may be modified to yield either the alpha or beta anomer. Both anomeric forms have shown the same antitumor activity.

1 Weigele, M.; De Bernado, S.; A synthesis of pyrazomycins. J Org Chem 1976, 41, 287-290.
2 Imbach, J.L.; Montero, J.L.; Rodriguez, M.; Sur une nouvelle voie de synthese de la R.F.C.N.U. Eur J Med Chem - Chim Ther 1977, 12, 408-412.
3 Eastland, G.; Bofumustine. Drugs Fut 1984, 9, 9, 641.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(B) 16170 1,2-dichloroethane 107-06-2 C2H4Cl2 详情 详情
(A) 18941 p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride 122-04-3 C7H4ClNO3 详情 详情
(I) 17718 (3aR,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-ol C8H14O5 详情 详情
(II) 34287 [(3aR,4R,6aR)-2,2-dimethyl-6-[(4-nitrobenzoyl)oxy]tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl 4-nitrobenzoate C22H20N2O11 详情 详情
(III) 34288 [(3aS,4R,6aR)-6-bromo-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl 4-nitrobenzoate C15H16BrNO7 详情 详情
(IV) 34289 [(3aR,4R,6aR)-6-isocyanato-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl 4-nitrobenzoate C16H16N2O8 详情 详情
(V) 34290 [(3aR,4R,6aR)-6-([[(2-chloroethyl)amino]carbonyl]amino)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl 4-nitrobenzoate C18H22ClN3O8 详情 详情
Extended Information