|
【结 构 式】 
|
【分子编号】28980 【品名】(4aR,6R,7R,7aS)-6-(6-amino-9H-purin-9-yl)-2,7-dihydroxytetrahydro-4H-2lambda(5)-furo[3,2-d][1,3,2]dioxaphosphinin-2-one 【CA登记号】60-92-4 |
【 分 子 式 】C10H12N5O6P 【 分 子 量 】329.209142 【元素组成】C 36.48% H 3.67% N 21.27% O 29.16% P 9.41% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of adenosine-3',5'-cyclic phosphate (I) with butyric anhydride (II) in the presence of triethylamine gives N6,2'-O-dibutyryladenosine-3',5'-cyclic phosphate (III), which is then treated with Na-type Amberlite IR-120 B.
| 【1】 JP 76113896 . |
| 【2】 Hirayama, T.; et al.; Improved methods of producing adenosine derivatives. JP 52039699 . |
| 【3】 JP 76095096 . |
| 【4】 Castaner, J.; Serradell, M.N.; Bucladesine Sodium. Drugs Fut 1985, 10, 2, 106. |
| 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) | 28980 | (4aR,6R,7R,7aS)-6-(6-amino-9H-purin-9-yl)-2,7-dihydroxytetrahydro-4H-2lambda(5)-furo[3,2-d][1,3,2]dioxaphosphinin-2-one | 60-92-4 | C10H12N5O6P | 详情 | 详情 |
| (II) | 28981 | 1-propoxypropane | 111-43-3 | C6H14O | 详情 | 详情 |
| (III) | 28982 | (4aR,6R,7R,7aR)-6-[6-(butyrylamino)-9H-purin-9-yl]-2-hydroxy-2-oxotetrahydro-4H-2lambda(5)-furo[3,2-d][1,3,2]dioxaphosphinin-7-yl butyrate | C18H24N5O8P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Direct chlorination of adenosine 3',5'-cyclic phosphate (I) was carried out by treatment with anhydrous HCl and m-chloroperbenzoic acid (m-CPBA) in DMF or with N-chlorosuccinimide and NaCl in aqueous HOAc. Chlorination of adenosine (II) was achieved by treatment with HCl in the presence of m-CPBA or in the absence of the oxidating reagent m-CPBA at a higher temperature and longer reaction times. The resultant 8-chloroadenosine (III) was converted to the monophosphate (IV) by means of POCl3, and this was further cyclized to the title compound using DCC. 8-Chloroadenosine monophosphate (IV) was also accessible by chlorination of adenosine monophosphate (V). Optionally, the chlorinated adenosine (III) was directly converted to the title cyclic phosphate by phosphorylation with POCl3 in the presence of NaOH in triethyl phosphate as the solvent.
| 【1】 Woo, N.-T.; et al.; The facile and efficient synthesis of 8-chloroadenosine 3',5'-cyclic monophosphate by phosphorylative cyclization of 8-chloroadenosine and its characterization by 1H and 13C NMR spectroscopy. Arch Pharmacal Res 1997, 20, 2, 176. |
| 【2】 Robins, R.K.; Revankar, G.R.; Chang, Y. (Nucleic Acid Res. Inst., Costa Mesa); Treatment of malignant tumours with 8-chloroadenosine 3'-5'-cyclic phosphate, 8-aminoadenosine 3',5'-cyclic phosphate and preparation thereof. EP 0499291; WO 8905648 . |
| 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) | 28980 | (4aR,6R,7R,7aS)-6-(6-amino-9H-purin-9-yl)-2,7-dihydroxytetrahydro-4H-2lambda(5)-furo[3,2-d][1,3,2]dioxaphosphinin-2-one | 60-92-4 | C10H12N5O6P | 详情 | 详情 |
| (II) | 11988 | Adenosine; (2R,3R,4S,5R)-2-(6-Amino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 58-61-7 | C10H13N5O4 | 详情 | 详情 |
| (III) | 59293 | (3R,4S,5R)-2-(6-amino-8-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C10H12ClN5O4 | 详情 | 详情 | |
| (IV) | 59294 | [(2R,3S,4R)-5-(6-amino-8-chloro-9H-purin-9-yl)-3,4-dihydroxytetrahydro-2-furanyl]methyl dihydrogen phosphate | C10H13ClN5O7P | 详情 | 详情 | |
| (V) | 59295 | [(2R,3S,4R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydro-2-furanyl]methyl dihydrogen phosphate | C10H14N5O7P | 详情 | 详情 |