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【结 构 式】 
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【分子编号】32802 【品名】1,3-dioxolan-2-one 【CA登记号】96-49-1 |
【 分 子 式 】C3H4O3 【 分 子 量 】88.06296 【元素组成】C 40.92% H 4.58% O 54.5% |
合成路线1
该中间体在本合成路线中的序号：(VII)By condensation of 2-aminomethyl-1,4-benzodioxane (I) with 2,6-dimethoxyphenoxyethyl chloride (II) performed by heating at 160 C or by means of K2CO3 in refluxing CHCl3 - water. The starting products (I) and (II) are prepared as follows: 1) The reaction of 2-chloromethyl-1,4-benzodioxane (III) with potassium phthalimide (IV) in refluxing DMF gives 2-phthalimidomethyl-1,4-benzodioxane (V), which is then treated with hydrazine hydrate (A) in refluxing 2-ethoxyethanol to give (I). 2) The condensation of 2,6-dimethoxyphenol (VI) with ethylene carbonate (VII) by means of K2CO3 in refluxing toluene gives 2,6-dimethoxyphenoxyethanol (VIII), which is then refluxed with SOCl2 to afford (II).
| 【1】 US 3472874 . |
| 【2】 Castaner, J.; Serradell, M.N.; Hillier, K.; Blancafort, P.; WB-4101. Drugs Fut 1979, 4, 5, 369. |
| 【3】 Green, P.N.; et al.; Synthesis and pharmacological properties of a series of 2-(substituted-aminoethyl)-1,4-benzodioxanes. J Med Chem 1969, 12, 2, 326-329. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 27334 | N-(2,5-dichloropentyl)-2-methoxy-5-[methyl(methylsulfonyl)amino]benzamide | C15H22Cl2N2O4S | 详情 | 详情 | |
| (I) | 39477 | 2,3-dihydro-1,4-benzodioxin-2-ylmethanamine; 2,3-dihydro-1,4-benzodioxin-2-ylmethylamine | C9H11NO2 | 详情 | 详情 | |
| (II) | 39479 | 2-(2-chloroethoxy)-1,3-dimethoxybenzene; 2-(2-chloroethoxy)-3-methoxyphenyl methyl ether | C10H13ClO3 | 详情 | 详情 | |
| (III) | 39475 | 2-(chloromethyl)-2,3-dihydro-1,4-benzodioxine | 2164-33-2 | C9H9ClO2 | 详情 | 详情 |
| (IV) | 27890 | Potassium phthalimide | 1074-82-4 | C8H4KNO2 | 详情 | 详情 |
| (V) | 39476 | 2-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1H-isoindole-1,3(2H)-dione | C17H13NO4 | 详情 | 详情 | |
| (VI) | 20228 | 2,6-dimethoxyphenol | 91-10-1 | C8H10O3 | 详情 | 详情 |
| (VII) | 32802 | 1,3-dioxolan-2-one | 96-49-1 | C3H4O3 | 详情 | 详情 |
| (VIII) | 39478 | 2-(2,6-dimethoxyphenoxy)-1-ethanol | C10H14O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)This compound can be obtained by several related ways: 1) The reaction of 2-thioxo-1,3-dithiole-4,5-dicarboxylic acid (I) with methyl iodide in refluxing nitromethane gives 2-(methylsulfanyl)-1,3-dithiolium iodide (II), which is finally condensed with diisopropyl malonate (III), by means of NaH in refluxing THF. 2) The cyclization of sodium acetylide (IV) with sulfur and carbon disulfide gives 1,3-dithiole-2-thione (V), which is treated first with dimethyl sulfate and then with sodium perchlorate yielding 2-(methylsulfanyl)-1,3-dithiolium perchlorate (V). Finally, this compound is condensed with diisopropyl malonate (III) by means of NaH as before. 3) 1,3-Dithiole-2-thione (V) can also be obtained by cyclization of ethylene carbonate (VII) with carbon disulfide by means of K2CO3 and hexabutyldistannathiane. 4) 1,3-Dithiole-2-thione (V) can also be obtained by cyclization of ethylene trithiocarbonate (VIII) with acetylene at 110-45 C, although with low yields. 5) The selective hydrolysis of 2-(4-acetoxy-1,3-dithiol-2-ylidene)malonic acid diisopropyl ester (IX) gives the corresponding 4-hydroxy derivative (X), which is finally dehydrated with either, chlorosulfonic acid or sulfuric acid or thionyl chloride and DBU or phosphorous trichloride or phosphorous oxychloride.
| 【1】 Fujinami, T.; et al.; The preparation of cyclic dithia and thiaza compounds by the reaction of potassium carbonate with heterocumulenes and alkylene dibromides or carbonate catalyzed by organostannyl compounds. Bull Chem Soc Jpn 1982, 55, 4, 1174. |
| 【2】 Mayer, R.; et al.; Synthesis of 1,3-dithiol-2-thiones (' Isotrithione'). Angew Chem. Int Ed Engl 1964, 76, 3, 143. |
| 【3】 Jones, F.N.; O'Connor, B.R.; Reactions of ethylene di- and trithiocarbonates with acetylenes. Anomalous reaction with bromocyanoacetylene to give a thioacyl bromide. J Org Chem 1970, 35, 6, 2002. |
| 【4】 Kurono, H.; Hirano, A.; Taninaka, K. (Nihon Nohyaku Co., Ltd.); 1,3-Dithiol-2-ylidene malonic esters. DE 2545569; US 4035387 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 23634 | acetylene | 74-86-2 | C2H2 | 详情 | 详情 | |
| (I) | 34902 | 2-thioxo-1,3-dithiole-4,5-dicarboxylic acid | C5H2O4S3 | 详情 | 详情 | |
| (II) | 34903 | 1,3-dithiol-2-ylidene(methyl)sulfonium iodide | C4H5IS3 | 详情 | 详情 | |
| (III) | 30735 | diisopropyl malonate | 13195-64-7 | C9H16O4 | 详情 | 详情 |
| (IV) | 34904 | ethynylsodium | 1066-26-8 | C2HNa | 详情 | 详情 |
| (V) | 34905 | 1,3-dithiole-2-thione | 930-35-8 | C3H2S3 | 详情 | 详情 |
| (VI) | 34906 | 1,3-dithiol-2-ylidene(methyl)sulfonium perchlorate | C4H5ClO4S3 | 详情 | 详情 | |
| (VII) | 32802 | 1,3-dioxolan-2-one | 96-49-1 | C3H4O3 | 详情 | 详情 |
| (VIII) | 34907 | 1,3-dithiolane-2-thione | 822-38-8 | C3H4S3 | 详情 | 详情 |
| (IX) | 34908 | diisopropyl 2-[4-(acetoxy)-1,3-dithiolan-2-ylidene]malonate | C14H20O6S2 | 详情 | 详情 | |
| (X) | 34909 | diisopropyl 2-(4-hydroxy-1,3-dithiolan-2-ylidene)malonate | C12H18O5S2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XI)This compound has been obtained by several related ways: 1) The reaction of ethyl butyrylacetate (I) with triethyl orthoformate and Ac2O gives acrylate (II), which by reaction with o-toluidine (III) yields the aminoacrylate (IV). The cyclization of (IV) by heating at 255 C in diphenyl ether affords the quinolone (V), which is treated with refluxing POCl3 to give 1-(4-chloro-8-methoxyquinolin-3-yl)-1-butanone (VI). The demethylation of (VI) with AlCl3 or BBr3 yields the 8-hydroxyquinoline (VII), which is condensed with o-toluidine (VIII) in refluxing dioxane affording 1-[8-hydroxy-4-(2-methylphenylamino)quinolin-3-yl-1-butanone (IX). Finally, this compound is condensed with 2-bromomethanol (X) by means of potassium tert-butoxide or with ethylene carbonate (XI) by means of K2CO3. 2) The condensation of chloroquinoline (VI) with o-toluidine (VIII) in refluxing dioxane gives 1-[8-methoxy-4-(2-methylphenylamino)quinolin-3-yl-1-butanone (XII), which is demethylated with AlCl3 or BBr3 as before yielding the previously reported 1-[8-hydroxy-4-(2-methylphenylamino)quinolin-3-yl-1-butanone (IX).
| 【1】 Atkins, R.J.; et al.; Synthetic routes to quinoline derivatives: Novel syntheses of 3-butyryl-8-methoxy-4-[(2-methylphenyl)amini]quinoline and 3-butyryl-8-(2-hydroxyethoxy)-4-[(2-methylphenyl)amino]quin. Org Process Res Dev 1997, 1, 3, 185. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 21304 | Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether | 122-51-0 | C7H16O3 | 详情 | 详情 | |
| (I) | 12516 | ethyl 3-oxohexanoate; ethyl butyrylacetate | 3249-68-1 | C8H14O3 | 详情 | 详情 |
| (II) | 12517 | ethyl (E)-2-butyryl-3-ethoxy-2-propenoate | C11H18O4 | 详情 | 详情 | |
| (III) | 25193 | 2-methoxyphenylamine; 2-methoxyaniline | 517-28-2 | C7H9NO | 详情 | 详情 |
| (IV) | 12518 | ethyl (Z)-2-butyryl-3-(2-methoxyanilino)-2-propenoate | C16H21NO4 | 详情 | 详情 | |
| (V) | 12519 | 3-Butyryl-8-methoxy-4(1H)-quinolinone | C14H15NO3 | 详情 | 详情 | |
| (VI) | 12520 | 1-(4-Chloro-8-methoxy-3-quinolinyl)-1-butanone | C14H14ClNO2 | 详情 | 详情 | |
| (VII) | 32800 | 1-(4-chloro-8-hydroxy-3-quinolinyl)-1-butanone | C13H12ClNO2 | 详情 | 详情 | |
| (VIII) | 15511 | o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine | 95-53-4 | C7H9N | 详情 | 详情 |
| (IX) | 32801 | 1-[8-hydroxy-4-(2-toluidino)-3-quinolinyl]-1-butanone | C20H20N2O2 | 详情 | 详情 | |
| (X) | 10059 | Ethylene bromohydrin; 2-Bromo-1-ethanol | 540-51-2 | C2H5BrO | 详情 | 详情 |
| (XI) | 32802 | 1,3-dioxolan-2-one | 96-49-1 | C3H4O3 | 详情 | 详情 |
| (XII) | 32799 | 1-[8-methoxy-4-(2-toluidino)-3-quinolinyl]-1-butanone | C21H22N2O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)An optimized process for large-scale production of adefovir dipivoxil has been reported: The reaction of adenine (I) with 1,3-dioxolan-2-one (II) by means of NaOH in hot DMF gives 9-(2-hydroxyethyl)adenine (III), which is condensed with diethyl p-toluenesulfonyloxymethylphosphonate (IV) by means of sodium tert-butoxide, (instead of NaH, originally used) in DMF yielding 9-[2-(diethylphosphonomethoxy)ethyl]adenine (V). The hydrolysis of intermediate (V) by means of TMS-Br in hot acetonitrile affords the phosphonic acid (VI), which is finally condensed with chloromethyl pivalate (VII) by means of triethylamine in hot N-methylpyrrolidine.
| 【1】 Dudzinski, P.W.; Kelly, D.E.; Yu, R.H.; Rohloff, J.C.; Schultze, L.M.; Process optimization in the synthesis of 9-[2-(diethylphosphonomethoxy)ethyl]adenine: Replacement of sodium hydride with sodium tert-butoxide as the base for oxygen alkylation. Org Process Res Dev 1999, 3, 1, 53. |
| 【2】 Kelly, D.E.; Lee, T.T.K.; Prisbe, E.J.; Schultze, L.M.; Arimilli, M.N.; Manes, L.V.; Munger, J.D. Jr. (Gilead Sciences Inc.); Nucleotide analog compsns.. WO 9904774 . |
| 【3】 Dahl, T.C.; Yuan, L.-C.J. (Gilead Sciences Inc.); Pharmaceutical formulations. WO 0035460 . |
| 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) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (II) | 32802 | 1,3-dioxolan-2-one | 96-49-1 | C3H4O3 | 详情 | 详情 |
| (III) | 39672 | 2-(6-amino-9H-purin-9-yl)-1-ethanol | C7H9N5O | 详情 | 详情 | |
| (IV) | 12702 | (diethoxyphosphoryl)methyl 4-methylbenzenesulfonate | 31618-90-3 | C12H19O6PS | 详情 | 详情 |
| (V) | 39673 | diethyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate | C12H20N5O4P | 详情 | 详情 | |
| (VI) | 16165 | [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonic acid | C8H12N5O4P | 详情 | 详情 | |
| (VII) | 16166 | chloromethyl pivalate | 18997-19-8 | C6H11ClO2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)The intermediate dicyclic carbonate (VI) was prepared by two alternative procedures: Erythromycin A (I) was converted into 11,12-cyclic carbonate (II) upon treatment with ethylene carbonate (II). Reduction of (II) with NaBH4 afforded the 9-dihydroerythromicyn derivative (III), which was protected at the 2'-hydroxyl group of the cladinose moiety by acetylation with Ac2O in acetone. Conversion of the resulting acetylated compound (V) to the corresponding 6,9;11,12-dicyclic carbonate was achieved by reaction with either diphosgene or triphosgene in the presence of pyridine, and the subsequent hydrolysis of the 2'-acetate in MeOH at room temperature furnished intermediate (VI). In a shorter procedure, 2'-O-acetyl-9-dihydroerythromycin A (VII) was reacted with 1,1'-carbonyldiimidazole and NaH to give the corresponding dicyclic carbonate. The acetate ester was then hydrolyzed to (VI) by treatment with MeOH.
| 【1】 Morimoto, S.; Sugiyama, H.; Tanikawa, T.; Kashimura, M.; Asaka, T.; Suzuki, K.; Adachi, T.; Akashi, T.; Synthesis and antibacterial activitis of unique acyclides: 3-O-Acyl-5-O-desosaminylerythronolide 6,9;11,12-dicarbonates. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F2160. |
| 【2】 Asaka, T.; Tanikawa, T.; Ishii, T.; Kashimura, M. (Taisho Pharmaceutical Co., Ltd.); Erythromycin A derivs.. WO 9813373 . |
| 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) | 33087 | (3R,4R,5R,6R,7R,9R,11R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-14-ethyl-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13-hexamethyl-2,10-oxacyclotetradecanedione; Erythromycin A | 114-07-8 | C37H67NO13 | 详情 | 详情 |
| (II) | 32802 | 1,3-dioxolan-2-one | 96-49-1 | C3H4O3 | 详情 | 详情 |
| (III) | 33088 | (3aR,4R,7R,8R,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11-hydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyloctahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecine-2,6,14(3aH,7H)-trione; (3aR,4R,7R,8R,9R,10R,11R,13R,15R,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11-hydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyloctahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecine-2,6,14(3aH,7H)-trione | C38H65NO14 | 详情 | 详情 | |
| (IV) | 33089 | (3aR,4R,7R,8R,9R,10R,11R,13R,15S,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11,14-dihydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyldecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecine-2,6(3aH)-dione; (3aR,4R,7R,8R,9R,10R,11R,13R,15S,15aR)-10-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4-ethyl-11,14-dihydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyldecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecine-2,6(3aH)-dione | C38H67NO14 | 详情 | 详情 | |
| (V) | 33090 | (2S,3R,4S,6R)-2-[((3aR,4R,7R,8R,9R,10R,11R,13R,15S,15aR)-4-ethyl-11,14-dihydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyl-2,6-dioxododecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecin-10-yl)oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate; (2S,3R,4S,6R)-2-[((3aR,4R,7R,8R,9R,10R,11R,13R,15S,15aR)-4-ethyl-11,14-dihydroxy-8-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3a,7,9,11,13,15-hexamethyl-2,6-dioxododecahydro-4H-[1,3]dioxolo[4,5-c]oxacyclotetradecin-10-yl)oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate | C40H69NO15 | 详情 | 详情 | |
| (VI) | 33091 | (2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione; (2S,3R,7R,8R,11R,12R,13R,14R,15R,19R)-14-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-8-ethyl-12-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-2,7,11,13,15,19-hexamethyl-4,6,9,16,18-pentaoxatricyclo[13.3.2.0(3,7)]icosane-5,10,17-trione | C39H65NO15 | 详情 | 详情 | |
| (VII) | 33092 | (2S,3R,4S,6R)-4-(dimethylamino)-2-[((3R,4R,5R,6R,7R,9R,11S,12R,13S,14R)-14-ethyl-7,10,12,13-tetrahydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13-hexamethyl-2-oxooxacyclotetradecanyl)oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate; (2S,3R,4S,6R)-4-(dimethylamino)-2-[((3R,4R,5R,6R,7R,9R,11S,12R,13S,14R)-14-ethyl-7,10,12,13-tetrahydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13-hexamethyl-2-oxooxacyclotetradecanyl)oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate | C39H71NO14 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(II)Treatment of adenosine (I) with ethylene carbonate (II) in the presence of NaOH in refluxing DMF gives 9-(2-hydroxyethyl)adenosine (III). Diethyl phosphite (IV) is then condensed with formaldehyde, followed by reaction with p-toluenesulfonyl chloride and Et3N to afford diethyl (tosyloxymethyl)phosphonate (V). Subsequent condensation of tosylate (V) with (III) in the presence of t-BuONa gives the phosphonyloxymethoxyethyl adenosine (PMEA) diethyl ester (VI), which is hydrolyzed to the corresponding phosphonic acid adefovir (VII) by means of in situ-generated iodotrimethylsilane. The condensation of phosphonic acid (VII) with 1(S)-(3-chlorophenyl)-1,3-propanediol (VIII) utilizing DCC/pyridine leads to the cyclic phosphonate (IX) as a roughly equimolecular mixture of diastereoisomers, which can be chromatographically separated to furnish the title cis-isomer pradefovir. In an improved procedure, activation of adefovir (VII) with oxalyl chloride and N,N-diethylformamide generates the formamidine-protected phosphonyl dichloridate (X), which upon condensation with diol (VIII) at low temperature gives the cyclic phosphonate (XI) as a mixture in which the desired cis-diastereoisomer predominates. After hydrolysis of the formamidine (XI) with ethanolic AcOH, recrystallization as the corresponding mesylate salt provides the title adefovir prodrug in high diastereomeric excess (1-5). Scheme 1.
| 【1】 Kopcho, J.J., Matelich, M.C., Reddy, K.R., Ugarkar, B.G. (Metabasis Therapeutics, Inc.). Process for preparation of cyclic prodrugs of PMEA and PMPA. JP 2005525422, US 2003225277, WO 2003095665. |
| 【2】 Erion, M.D., Kopcho, J.J., Matelich, M.C., Reddy, K.R. (Metabasis Therapeutics, Inc.). Novel phosphonic acid based prodrugs of PMEA and its analogues. EP 1532157, US 2003229225, WO 2004037161. |
| 【3】 Reddy, K.R., Matelich, M.C., Ugarkar, B.G. et al. HepDirect prodrugs of adefovir: Design, synthesis and optimization. 227th ACS Natl Meet (March 28-April 1, Anaheim) 2004, Abst MEDI- 27. |
| 【4】 Martin, K. (Metabasis Therapeutics, Inc.). Lewis acid mediated synthesis of cyclic esters. CA 2565966, EP 1753762, US 2005282782, WO 2005123729. |
| 【5】 Erion, M.D., Reddy, K.R., Boyer, S.H. et al. Design, synthesis, and characterization of a series of cytochrome P450 3A-activated prodrugs (HepDirect prodrugs) useful for targeting phospho(on)ate-based drugs to the liver. J Am Chem Soc 2004, 126(16): 5154-63. |
| 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) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (II) | 32802 | 1,3-dioxolan-2-one | 96-49-1 | C3H4O3 | 详情 | 详情 |
| (III) | 39672 | 2-(6-amino-9H-purin-9-yl)-1-ethanol | C7H9N5O | 详情 | 详情 | |
| (IV) | 12714 | diethyl phosphonate; diethyl phosphite | 762-04-9 | C4H11O3P | 详情 | 详情 |
| (V) | 12702 | (diethoxyphosphoryl)methyl 4-methylbenzenesulfonate | 31618-90-3 | C12H19O6PS | 详情 | 详情 |
| (VI) | 39673 | diethyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate | C12H20N5O4P | 详情 | 详情 | |
| (VII) | 16165 | [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonic acid | C8H12N5O4P | 详情 | 详情 | |
| (VIII) | 65232 | 1(S)-(3-chlorophenyl)-1,3-propanediol | C9H11ClO2 | 详情 | 详情 | |
| (IX) | 65233 | C17H19ClN5O4P | 详情 | 详情 | ||
| (X) | 65234 | C13H19Cl2N6O2P | 详情 | 详情 | ||
| (XI) | 65235 | C22H28ClN6O4P | 详情 | 详情 |