【结 构 式】 |
【分子编号】49119 【品名】3-(acetoxy)-2-azidopropyl acetate 【CA登记号】 |
【 分 子 式 】C7H11N3O4 【 分 子 量 】201.18216 【元素组成】C 41.79% H 5.51% N 20.89% O 31.81% |
合成路线1
该中间体在本合成路线中的序号:(II)2-Amino-1,3-propanediol (I) was reacted with in situ generated trifluoromethanesulfonyl azide, and the resulting 2-azido compound was purified by chromatography after conversion to the diacetate ester (II). Deacetylation of (II) with sodium methoxide gave 2-azido-1,3-propanediol (III), which was condensed with tosylate (IV) in the presence of NaH to produce the dihydroxyether (V). The primary alcohol group of (V) was then protected as the mono-silyl derivative (VI) employing tert-butyldiphenylsilyl chloride. After acylation of the free hydroxyl group of (VI) with the unsaturated acid (VII), the resulting ester (VIII) was desilylated by using HF in acetonitrile to yield alcohol (IX). The phosphorylating reagent (XII) was prepared by treatment of allyl phosphorodiamidite (X) with N-Boc-ethanolamine (XI). Phosphitylation of alcohol (IX) with phosphoramidite (XII), followed by oxidation of the intermediate phosphite ester with oxone , furnished phosphate (XIII). The azido group of (XIII) was then reduced to the corresponding amine (XIV) by employing (PhS)2Sn.
【1】 Rossignol, D.P.; Ishizaka, S.T.; Nault, A.; Lewis, M.; Rose, J.; McGuiness, P.; Hawkins, L.D. (Eisai Co., Ltd.); Immunological adjuvant cpd.. EP 1147117; US 6290973; WO 0044758 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 23333 | 2-amino-1,3-propanediol; serinol | 534-03-2 | C3H9NO2 | 详情 | 详情 |
(II) | 49119 | 3-(acetoxy)-2-azidopropyl acetate | C7H11N3O4 | 详情 | 详情 | |
(III) | 49120 | 2-azido-1,3-propanediol | C3H7N3O2 | 详情 | 详情 | |
(IV) | 49121 | (3R)-3-hydroxydecyl 4-methylbenzenesulfonate | C17H28O4S | 详情 | 详情 | |
(V) | 49122 | (3R)-1-(2-azido-3-hydroxypropoxy)-3-decanol | C13H27N3O3 | 详情 | 详情 | |
(VI) | 49123 | (3R)-1-(2-azido-3-[[tert-butyl(diphenyl)silyl]oxy]propoxy)-3-decanol | C29H45N3O3Si | 详情 | 详情 | |
(VII) | 49124 | (Z)-5-dodecenoic acid | C12H22O2 | 详情 | 详情 | |
(VIII) | 49125 | (1R)-1-[2-(2-azido-3-[[tert-butyl(diphenyl)silyl]oxy]propoxy)ethyl]octyl (Z)-5-dodecenoate | C41H65N3O4Si | 详情 | 详情 | |
(IX) | 49126 | (1R)-1-[2-(2-azido-3-hydroxypropoxy)ethyl]octyl (Z)-5-dodecenoate | C25H47N3O4 | 详情 | 详情 | |
(X) | 49127 | C15H33N2OP | 详情 | 详情 | ||
(XI) | 32500 | tert-butyl 2-hydroxyethylcarbamate | 26690-80-2 | C7H15NO3 | 详情 | 详情 |
(XII) | 49128 | C16H33N2O4P | 详情 | 详情 | ||
(XIII) | 49129 | (1R)-9-(allyloxy)-6-azido-1-heptyl-16,16-dimethyl-9,14-dioxo-4,8,10,15-tetraoxa-13-aza-9lambda(5)-phosphaheptadec-1-yl (Z)-5-dodecenoate | C35H65N4O9P | 详情 | 详情 | |
(XIV) | 49130 | (1R)-9-(allyloxy)-6-amino-1-heptyl-16,16-dimethyl-9,14-dioxo-4,8,10,15-tetraoxa-13-aza-9lambda(5)-phosphaheptadec-1-yl (Z)-5-dodecenoate | C35H67N2O9P | 详情 | 详情 |