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【结 构 式】 
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【分子编号】19248 【品名】diethyl hydroxymethylphosphonate 【CA登记号】3084-40-0 |
【 分 子 式 】C5H13O4P 【 分 子 量 】168.129582 【元素组成】C 35.72% H 7.79% O 38.06% P 18.42% |
合成路线1
该中间体在本合成路线中的序号：(XXIII)3) The catalytic hydrogenation of (S)-glycidol (XVI) over Pd/C gives the (R)-1,2-propanediol (XVII), which is esterified with diethyl carbonate (XVIII)/NaOEt, yielding the cyclic carbonate (XIX). The reaction of (XIX) with adenine (V) by means of NaOH in DMF affords 9-[2(R)-hydroxypropyl]adenine (VII), which is condensed with tosyloxymethylphosphonic acid diethyl ester (XX) by means of lithium tert-butoxide in THF, giving 9-[2(R)-(diethoxyphosphorylmethoxy)propyl]adenine (XXI). Finally, this compound is hydrolyzed with bromotrimethylsilane as before. Compound (XX) is obtained by reaction of diethyl phosphite (XXII) with paraformaldehyde, yielding hydroxy- methylphosphonic acid diethyl ester (XXIII), which is finally tosylated as usual.
| 【1】 Leone-Bay, A.; et al.; 4-(4-Salicyloylaminophenyl)butyric acid as a novel oral delivery agent for recombinant human growth hormone. 211th ACS Natl Meet (March 24-28, New Orleans) 1996, Abst MEDI 006. |
| 【2】 Schultze, L.M.; Chapman, H.H.; Dubree, N.J.P.; et al.; Practical synthesis of the anti-HIV drug, PMPA. Tetrahedron Lett 1998, 39, 14, 1853. |
| 【3】 Sorbera, L.A.; Castañer, J.; (R)-PMPA and Bis(POC)PMPA. Drugs Fut 1998, 23, 12, 1279. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (VII) | 19232 | (2S)-1-(6-amino-9H-purin-9-yl)-2-propanol | C8H11N5O | 详情 | 详情 | |
| (XVI) | 19241 | (2S)oxiranylmethanol | 60456-23-7 | C3H6O2 | 详情 | 详情 |
| (XVII) | 19242 | (2S)-1,2-propanediol | 4254-15-3 | C3H8O2 | 详情 | 详情 |
| (XVIII) | 17470 | diethyl carbonate; diethylcarbonate | 105-58-8 | C5H10O3 | 详情 | 详情 |
| (XIX) | 19244 | (4S)-4-methyl-1,3-dioxolan-2-one | C4H6O3 | 详情 | 详情 | |
| (XX) | 12702 | (diethoxyphosphoryl)methyl 4-methylbenzenesulfonate | 31618-90-3 | C12H19O6PS | 详情 | 详情 |
| (XXI) | 19246 | diethyl [[(1S)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy]methylphosphonate | C13H22N5O4P | 详情 | 详情 | |
| (XXII) | 12714 | diethyl phosphonate; diethyl phosphite | 762-04-9 | C4H11O3P | 详情 | 详情 |
| (XXIII) | 19248 | diethyl hydroxymethylphosphonate | 3084-40-0 | C5H13O4P | 详情 | 详情 |