|
【结 构 式】 
|
【分子编号】48722 【品名】[(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl trityl ether; 6-chloro-9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purine 【CA登记号】 |
【 分 子 式 】C29H24ClFN4O2 【 分 子 量 】514.9864232 【元素组成】C 67.64% H 4.7% Cl 6.88% F 3.69% N 10.88% O 6.21% |
合成路线1
该中间体在本合成路线中的序号：(III)A practical synthesis of lodenosine has been reported: Selective tritylation of the chloropurine derivative (I) at the primary OH group by treatment with trityl chloride, TEA and DMAP in DMF gives the 5'-O-trityl ether (II), which is fluorinated with diethylamino sulfur trifluoride (DAST) and pyridine in dichloromethane to yield the 2'-beta-fluoro derivative (III). Reaction of compound (III) with ammonia in THF affords the tritylated lodenosine derivative (IV), which is finally deprotected with 37% HCl in methanol/water.
| 【1】 Hirose, N.; Takamatsu, S.; Katayama, S.; Naito, M.; Izawa, K.; Maruyama, T.; Practical synthesis of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (FddA) via a purine 3'-deoxynucleoside. Tetrahedron Lett 2001, 42, 12, 2325. |
| 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) | 48720 | (2R,3R,5S)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3-furanol | C10H11ClN4O3 | 详情 | 详情 | |
| (II) | 48721 | (2R,3R,5S)-2-(6-chloro-9H-purin-9-yl)-5-[(trityloxy)methyl]tetrahydro-3-furanol | C29H25ClN4O3 | 详情 | 详情 | |
| (III) | 48722 | [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl trityl ether; 6-chloro-9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purine | C29H24ClFN4O2 | 详情 | 详情 | |
| (IV) | 29876 | 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-ylamine; 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-amine | C29H26FN5O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The reaction of inosine (I) with trimethyl orthoacetate and AcOH, followed by a treatment with acetyl bromide, gives 3'-beta-bromo-3'-deoxyinosine (II), which is debrominated by means of Bu3SnH and AIBN in toluene to yield 3'-deoxyinosine (III). The reaction of (III) with SOCl2 /DMF in refluxing dichloromethane or with POCl3 /TEA in refluxing acetonitrile yields the 6-chloropurine (IV), which is deacetylated with NaOMe in methanol to afford the dihydroxy compound (V). The selective tritylation of the primary OH group of (V) with Tr-Cl and collidine in acetonitrile provides the trityl ether (VI), which is fluorinated with diethylaminosulfur trifluoride (DAST) and pyridine in dichloromethane to give the 3'-beta-fluoro derivative (VII). The reaction of (VII) with ammonia in THF gives the tritylated fluoroadenosine (VIII), which is finally deprotected with HCl in methanol/water to provide the target lodenosine. Alternatively, conversion of (VII) into lodenosine can be performed by first removal of the trityl protecting group with HCl in MeOH/toluene yielding compound (IX), whose chlorine atom is finally displaced with ammonia in MeOH/toluene
| 【1】 Takamatsu, S.; et al.; 9-(2,3-Dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (FddA) via a purine 3'-deoxynucleoside. J Org Chem 2001, 66, 22, 7469. |
| 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) | 38013 | 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one | C10H12N4O5 | 详情 | 详情 | |
| (II) | 55505 | [(2R,3S,4S,5R)-4-(acetyloxy)-3-bromo-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C14H15BrN4O6 | 详情 | 详情 | |
| (III) | 55506 | (2R,3R,5S)-5-[(acetyloxy)methyl]-2-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C14H16N4O6 | 详情 | 详情 | |
| (IV) | 55507 | [(2S,4R,5R)-4-(acetyloxy)-5-(6-chloro-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C14H15ClN4O5 | 详情 | 详情 | |
| (V) | 48720 | (2R,3R,5S)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3-furanol | C10H11ClN4O3 | 详情 | 详情 | |
| (VI) | 48721 | (2R,3R,5S)-2-(6-chloro-9H-purin-9-yl)-5-[(trityloxy)methyl]tetrahydro-3-furanol | C29H25ClN4O3 | 详情 | 详情 | |
| (VII) | 48722 | [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl trityl ether; 6-chloro-9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purine | C29H24ClFN4O2 | 详情 | 详情 | |
| (VIII) | 29876 | 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-ylamine; 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-amine | C29H26FN5O2 | 详情 | 详情 | |
| (IX) | 17712 | [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methanol | C10H10ClFN4O2 | 详情 | 详情 |