• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】46264

【品名】[(3aR,5R,6S,6aR)-6-(benzyloxy)-5-ethynyl-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzyl ether; (3aR,5R,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-5-ethynyl-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole

【CA登记号】

【 分 子 式 】C24H26O5

【 分 子 量 】394.46744

【元素组成】C 73.08% H 6.64% O 20.28%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IV)

The oxidation of the hydroxymethyl group of 3,5-di-O-benzyl-4-C-(hydroxymethyl)-1,2-O-isopropylidene-alpha-D-ribo-pentofuranose (I) with oxalyl chloride and TEA in DMSO gives the aldehyde (II), which is treated with CBr4 and PPH3 in dichloromethane to yield the dibromovinyl compound (III). The reaction of (III) with BuLi in THF affords the ethynyl derivative (IV), which is silylated with Tes-Cl and BuLi in THF to provide the triethylsilylethynyl compound (V). Elimination of the acetonide group of (V) with HOAc and TFA gives the dihydroxycompound (VI), which is treated with Ac2O and pyridine, yielding the diacetate (VII). The condensation of the sugar(VII) with 5-fluorouracil (VIII) by means of Tms-OTf and N,O-bis(trimethylsilyl)acetamide in dichloroethane affords the adduct (IX), which is deacetylated with TEA in methanol to provide the hydroxy derivative (X). The debenzylation of (X) by means of BCl3 in dichloromethane furnishes the trihydroxy compound (XI), which is treated with acetyl bromide in acetonitrile to give the bromo diacetoxy derivative (XII). The debromination of (XII) is performed with Bu3SnH and AIBN in hot toluene, yielding the diacetate (XIII), which is condensed with 1,2,4-triazole (XIV) by means of 4-chlorophenyl dichlorophosphate in pyridine to afford the triazolopyrimidinone (XV). Finally, (XV) is converted into the target compound by cleavage of the triazole ring with NH4OH in dioxane and deacetylation with NaOH in methanol/water.

1 Kohgo, S.; Kitano, K.; Ohrui, H.; et al.; Synthesis of 4'-C-ethynyl-beta-D-arabino-and 4'-C-ethynyl-2'-deoxy-beta-D-ribo-pentofuranosylpyrimidines and -purines and evaluation of their anti-HIV activity. J Med Chem 2000, 43, 23, 4516.
2 Matsuoka, M.; Kodama, E.; Kitano, K.; Kohgo, S.; Mitsuya, H.; Ohrui, H. (Yamasa Shoyu Co., Ltd.); 4'-C-Ethynyl purine nucleosides. WO 0069876; WO 0069877 .
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) 30917 [(3aR,5S,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methanol C23H28O6 详情 详情
(II) 46262 (3aR,5R,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde C23H26O6 详情 详情
(III) 46263 (3aR,5R,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-5-(2,2-dibromovinyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole; [(3aR,5R,6S,6aR)-6-(benzyloxy)-5-(2,2-dibromovinyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzyl ether C24H26Br2O5 详情 详情
(IV) 46264 [(3aR,5R,6S,6aR)-6-(benzyloxy)-5-ethynyl-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzyl ether; (3aR,5R,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-5-ethynyl-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole C24H26O5 详情 详情
(V) 46265 [(3aR,5R,6S,6aR)-6-(benzyloxy)-2,2-dimethyl-5-[2-(triethylsilyl)ethynyl]tetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzyl ether; (2-[(3aR,5R,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]ethynyl)(triethyl)silane C30H40O5Si 详情 详情
(VI) 46266 (2S,3R,4S,5R)-4-(benzyloxy)-5-[(benzyloxy)methyl]-5-[2-(triethylsilyl)ethynyl]tetrahydro-2,3-furandiol C27H36O5Si 详情 详情
(VII) 46267 (2R,3R,4S,5R)-2-(acetoxy)-4-(benzyloxy)-5-[(benzyloxy)methyl]-5-[2-(triethylsilyl)ethynyl]tetrahydro-3-furanyl acetate C31H40O7Si 详情 详情
(VIII) 29341 (6R,9S,12S)-6-(cyclohexylmethyl)-12-[3-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]propyl]-9-(1H-indol-3-ylmethyl)-2,2-dimethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oic acid C38H53N7O8S 详情 详情
(IX) 46268 (2R,3R,4S,5R)-4-(benzyloxy)-5-[(benzyloxy)methyl]-2-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-5-[2-(triethylsilyl)ethynyl]tetrahydro-3-furanyl acetate C33H39FN2O7Si 详情 详情
(X) 46269 1-[(2R,3R,4S,5R)-4-(benzyloxy)-5-[(benzyloxy)methyl]-3-hydroxy-5-[2-(triethylsilyl)ethynyl]tetrahydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione C31H37FN2O6Si 详情 详情
(XI) 46270 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-5-[2-(triethylsilyl)ethynyl]tetrahydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione C17H25FN2O6Si 详情 详情
(XII) 46271 [(2R,3R,4R,5R)-3-(acetoxy)-4-bromo-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-[2-(triethylsilyl)ethynyl]tetrahydro-2-furanyl]methyl acetate C21H28BrFN2O7Si 详情 详情
(XIII) 46272 [(2R,3S,5R)-3-(acetoxy)-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-[2-(triethylsilyl)ethynyl]tetrahydro-2-furanyl]methyl acetate C21H29FN2O7Si 详情 详情
(XIV) 13135 1H-1,2,4-Triazole; 1,2,4-Triazole 288-88-0 C2H3N3 详情 详情
(XV) 46273 [(2R,3S,5R)-3-(acetoxy)-5-[5-fluoro-2-oxo-4-(1H-1,2,4-triazol-1-yl)-1(2H)-pyrimidinyl]-2-[2-(triethylsilyl)ethynyl]tetrahydro-2-furanyl]methyl acetate C23H30FN5O6Si 详情 详情
Extended Information