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【结 构 式】 
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【分子编号】48061 【品名】1-[3-(2,3-dihydro-1H-inden-5-yloxy)-2-[(2-methoxyethoxy)methyl]-3-oxopropyl]cyclopentanecarboxylic acid 【CA登记号】 |
【 分 子 式 】C22H30O6 【 分 子 量 】390.4766 【元素组成】C 67.67% H 7.74% O 24.58% |
合成路线1
该中间体在本合成路线中的序号：(IV)The known 2-(2-methoxyethoxymethyl)-3-[1-(phenacyloxycarbonyl)cyclopentyl]propanoic acid (I) was esterified with 5-indanol (II) by using EDC and HOBt to afford the indanyl ester (III). The phenacyl ester group was then reductively cleaved with Zn in HOAc to yield the racemic carboxylic acid (IV). Resolution of (IV) by means of (+)-pseudoephedrine provided the (S)-enantiomer (V). The chiral acid (V) was then coupled with benzyl cis-4-amino-1-cyclohexancarboxylate (VI) in the presence of EDC and HOBt to furnish amide (VII). The benzyl ester group of (VII) was finally cleaved by hydrogenolysis over Pd/C to give the title compound.
| 【1】 Williams, M.T.; Danilewicz, J.C. (Pfizer Inc.); Enantiomeric glutaramide diuretic agents. EP 0342850 . |
| 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) | 48058 | 3-(2-methoxyethoxy)-2-([1-[(2-oxo-2-phenylethoxy)carbonyl]cyclopentyl]methyl)propionic acid | C21H28O7 | 详情 | 详情 | |
| (II) | 48059 | 5-indanol | 1470-94-6 | C9H10O | 详情 | 详情 |
| (III) | 48060 | 2-oxo-2-phenylethyl 1-[3-(2,3-dihydro-1H-inden-5-yloxy)-2-[(2-methoxyethoxy)methyl]-3-oxopropyl]cyclopentanecarboxylate | C30H36O7 | 详情 | 详情 | |
| (IV) | 48061 | 1-[3-(2,3-dihydro-1H-inden-5-yloxy)-2-[(2-methoxyethoxy)methyl]-3-oxopropyl]cyclopentanecarboxylic acid | C22H30O6 | 详情 | 详情 | |
| (V) | 48062 | 1-[(2S)-3-(2,3-dihydro-1H-inden-5-yloxy)-2-[(2-methoxyethoxy)methyl]-3-oxopropyl]cyclopentanecarboxylic acid | C22H30O6 | 详情 | 详情 | |
| (VI) | 48063 | benzyl 4-aminocyclohexanecarboxylate | C14H19NO2 | 详情 | 详情 | |
| (VII) | 48064 | benzyl 4-[[(1-[(2S)-3-(2,3-dihydro-1H-inden-5-yloxy)-2-[(2-methoxyethoxy)methyl]-3-oxopropyl]cyclopentyl)carbonyl]amino]cyclohexanecarboxylate | C36H47NO7 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The reaction of adenosine (I) 2-acetoxyisobutyryl bromide (A) in acetonitrile/water gives a mixture of the 3-bromo (II) and 2-bromo nucleosides (III), which is treated with Dowex (OH), Amberlite (OH) or methanolic NaOMe to yield the epoxide (IV). Finally, this compound is reduced with LiEt3BH in THF/DMSO or LiAlH4 in THF to afford a mixture of the 2'-deoxy nucleoside (V) and the target compound that are separated by chromatography. Alternatively, the mixture of the nucleosides (II) and (III) is debrominated by reaction with Bu3SnH and AIBN in refluxing toluene to give the same mixture of (V) and the target compound that is separated as before.
| 【1】 Russell, A.F.; et al.; Reactions of 2-acyloxyisobutyryl halides with nucleosides. II. Reactions of adenosine. J Am Chem Soc 1973, 95, 12, 4025. |
| 【2】 Hansske, F.; Robins, M.J.; Regiospecific and stereoselective conversion of ribonucleosides to 3'-deoxynucleosides. A high yield three-stage synthesis of cordycepin from adenosine. Tetrahedron Lett 1985, 26, 36, 4295. |
| 【3】 Bazin, H.; Chattopadhyaya, J.; A convenient preparation of 3'-deoxyadenosine (cordycepin) and 9-[3'(R)-deuterio-beta-D-2'(R)-pentofuranosyl]-adenine. Synthesis 1985, 1108. |
| 【4】 Robins, M.J.; et al.; Nucleic acid related compounds. 88. Efficient conversions of ribonucleosides into their 2',3'-anhydro, 2'(and 3')-deoxy, 2',3'-didehydro-2',3'-dideoxy, and 2',3'-dideoxynucleoside analogues. J Org Chem 1995, 60, 24, 7902. |
| 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) | 49211 | 1-(bromocarbonyl)-2-methylpropyl acetate | C7H11BrO3 | 详情 | 详情 | |
| (I) | 11988 | Adenosine; (2R,3R,4S,5R)-2-(6-Amino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 58-61-7 | C10H13N5O4 | 详情 | 详情 |
| (II) | 49212 | (2R,3S,4S,5R)-2-(6-amino-9H-purin-9-yl)-4-bromo-5-[[(2,4,4-trimethyl-5-oxo-1,3-dioxolan-2-yl)oxy]methyl]tetrahydro-3-furanyl acetate | C18H22BrN5O7 | 详情 | 详情 | |
| (III) | 36390 | (2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-bromo-2-[[(2,4,4-trimethyl-5-oxo-1,3-dioxolan-2-yl)oxy]methyl]tetrahydro-3-furanyl acetate | C18H22BrN5O7 | 详情 | 详情 | |
| (IV) | 48061 | 1-[3-(2,3-dihydro-1H-inden-5-yloxy)-2-[(2-methoxyethoxy)methyl]-3-oxopropyl]cyclopentanecarboxylic acid | C22H30O6 | 详情 | 详情 | |
| (V) | 49213 | [(1S,2R,4R,5R)-4-(6-amino-9H-purin-9-yl)-3,6-dioxabicyclo[3.1.0]hex-2-yl]methanol | C10H11N5O3 | 详情 | 详情 |