【结 构 式】 |
【分子编号】46543 【品名】9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-amine; 9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-ylamine 【CA登记号】 |
【 分 子 式 】C13H19N5O2 【 分 子 量 】277.32636 【元素组成】C 56.3% H 6.91% N 25.25% O 11.54% |
合成路线1
该中间体在本合成路线中的序号:(VIII)A new synthetic route to famciclovir has been described: The alkylation of 2,2-dimethyl-1,3-dioxan-5-one (I) with vinylmagnesium bromide (II) in THF gives the 2,2-dimethyl-5-vinyl-1,3-dioxan-5-ol derivative (II), which is treated with methyl chloroformate in the same solvent to yield the mixed carbonate (IV). Condensation of (IV) with 6-chloropurine-2-amine (V) by means of 1,2-bis(diphenylphosphino)ethane (dppe) and tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3] in DMF at 80 °C for 7.5 h affords a 5:95 mixture of the N-7 (VI) and N-9 (VII) regioisomers, respectively. Hydrogenation of regioisomer (VII) with H2 over Pd/C in THF eliminates the 6-chlorine atom and reduces the exocyclic double bond giving the 2-aminopurine derivative (VIII), which is treated with HCl in methanol to remove the acetonide group affording diol (IX). Finally, this compound is acylated with acetic anhydride and DMAP/TEA in dichloromethane.
【1】 Geen, G.R.; Share, A.C.; Slater, G.R.; Ramsay, T.W.; Smith, N.M.; Freer, R.; A new route to famciclovir via palladium catalysed allylation. Tetrahedron 2000, 56, 26, 4589. |
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) | 46538 | 2,2-dimethyl-1,3-dioxan-5-one | C6H10O3 | 详情 | 详情 | |
(II) | 16524 | bromo(vinyl)magnesium | 1826-67-1 | C2H3BrMg | 详情 | 详情 |
(III) | 46539 | C8H13BrMgO3 | 详情 | 详情 | ||
(IV) | 46540 | 2,2-dimethyl-5-vinyl-1,3-dioxan-5-yl methyl carbonate | C10H16O5 | 详情 | 详情 | |
(V) | 11644 | 6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine | 10310-21-1 | C5H4ClN5 | 详情 | 详情 |
(VI) | 46541 | 6-chloro-7-[2-(2,2-dimethyl-1,3-dioxan-5-ylidene)ethyl]-7H-purin-2-ylamine; 6-chloro-7-[2-(2,2-dimethyl-1,3-dioxan-5-ylidene)ethyl]-7H-purin-2-amine | C13H16ClN5O2 | 详情 | 详情 | |
(VII) | 46542 | 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-ylidene)ethyl]-9H-purin-2-ylamine; 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-ylidene)ethyl]-9H-purin-2-amine | C13H16ClN5O2 | 详情 | 详情 | |
(VIII) | 46543 | 9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-amine; 9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-ylamine | C13H19N5O2 | 详情 | 详情 | |
(IX) | 11643 | 2-[2-(2-Amino-9H-purin-9-yl)ethyl]-1,3-propanediol | C10H15N5O2 | 详情 | 详情 |