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【结 构 式】 
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【分子编号】50276 【品名】1-benzyl-5-ethoxy-1,3-dihydro-2H-indol-2-one 【CA登记号】 |
【 分 子 式 】C17H17NO2 【 分 子 量 】267.32752 【元素组成】C 76.38% H 6.41% N 5.24% O 11.97% |
合成路线1
该中间体在本合成路线中的序号：(VII)Indolinone intermediate (VII): 1. The reductoalkylation of 4-ethoxyaniline (I) with benzaldehyde and NaBH4 in methanol gives the protected aniline (II), which is condensed with methoxymalonyl chloride (III) by means of TEA in dichloromethane to yield the malonamic derivative (IV). The reaction of (IV) with methanesulfonyl azide (V) and TEA affords the diazo compound (VI), which is finally submitted to a decarboxylative cyclization by means of Nafion H (a perfluorinated ion exchange resin) to provide the target indolinone intermediate (VII). 2. The condensation of the protected aniline (II) with diketene (VIII) by means of TEA in THF gives the 3-oxobutyramide (IX), which is treated with methanesulfonyl azide (V) and TEA to yield the diazo compound (X). The deacylation of (X) with KOH in acetonitrile affords the diazoacetamide (XI), which is finally cyclized to the target indolinone intermediate (VII) by means of Rh(OAc)2 in dichloromethane.
| 【1】 Venkatesan, H.; et al.; Total synthesis of SR 121463 A, a highly potent and selective vasopressin V2 receptor antagonist. J Org Chem 2001, 66, 11, 3653. |
| 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) | 45939 | 4-Aminophenetole; 1-Amino-4-ethoxybenzene; 4-Aminoethoxybenzene; 4-Ethoxyphenylamine; p-Phenetidine; 4-Ethoxyaniline | 156-43-4 | C8H11NO | 详情 | 详情 |
| (II) | 50271 | N-benzyl-4-ethoxyaniline; N-benzyl-N-(4-ethoxyphenyl)amine | C15H17NO | 详情 | 详情 | |
| (III) | 50272 | Malonic acid monomethyl ester chloride; Methyl (chloroformyl)acetate; Methyl malonyl chloride ;Methyl 3-chloro-3-oxopropionate | 37517-81-0 | C4H5ClO3 | 详情 | 详情 |
| (IV) | 50273 | methyl 3-(benzyl-4-ethoxyanilino)-3-oxopropanoate | C19H21NO4 | 详情 | 详情 | |
| (V) | 50274 | methanesulfonyl azide | CH3N3O2S | 详情 | 详情 | |
| (VI) | 50275 | C19H19N3O4 | 详情 | 详情 | ||
| (VII) | 50276 | 1-benzyl-5-ethoxy-1,3-dihydro-2H-indol-2-one | C17H17NO2 | 详情 | 详情 | |
| (VIII) | 11367 | 4-Methylene-2-oxetanone; Acetyl ketene | 674-82-8 | C4H4O2 | 详情 | 详情 |
| (IX) | 50277 | N-benzyl-N-(4-ethoxyphenyl)-3-oxobutanamide | C19H21NO3 | 详情 | 详情 | |
| (X) | 50278 | C19H19N3O3 | 详情 | 详情 | ||
| (XI) | 50279 | C17H17N3O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Assembly of the target compound: The reaction of methyl 3-bromopropionate (XVII) with ethylmagnesium bromide (XVIII) and Ti(iPrO)4 gives 1-(2-bromoethyl)cyclopropan-1-ol (XIX), which is brominated by NBS in CCl4 to yield 1,5-dibromo-3-pentanone (XX). The reaction of (XX) with ethylene glycol (XXI), HC(OEt)3 and PPTS affords the cyclic ketal (XXII), which is cyclized with the indolinone intermediate (VII) by means of NaH in DMF to provide the spiro compound (XXIII). The deprotection of (XXIII) with PPTS in acetone/water gives the spiranic diketone (XXIV), which is selectively reduced with NaBH4 in methanol to yield the spiro cyclohexanol (XXV). The condensation of (XXV) with 4-(2-chloroethyl)morpholine (XXVI) by means of NaH in hot toluene affords the corresponding ether (XXVII), which is debenzylated by means of Li/NH3 to provide intermediate (XXVIII) with a free NH group. Finally, the sulfonation of (XXVIII) with intermediate chlorosulfonyl benzamide (XVI) by means of potassium tert-butoxide gives the target sulfonyl benzamide compound.
| 【1】 Venkatesan, H.; et al.; Total synthesis of SR 121463 A, a highly potent and selective vasopressin V2 receptor antagonist. J Org Chem 2001, 66, 11, 3653. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 50276 | 1-benzyl-5-ethoxy-1,3-dihydro-2H-indol-2-one | C17H17NO2 | 详情 | 详情 | |
| (XVI) | 50284 | 4-[(tert-butylamino)carbonyl]-2-methoxybenzenesulfonyl chloride | C12H16ClNO4S | 详情 | 详情 | |
| (XVII) | 50285 | 3-Bromopropionic acid methyl ester; Methyl 3-bromopropionate | 3395-91-3 | C4H7BrO2 | 详情 | 详情 |
| (XVIII) | 24239 | bromo(ethyl)magnesium；ethylmagnesium bromide | 925-90-6 | C2H5BrMg | 详情 | 详情 |
| (XIX) | 50286 | 1-(2-bromoethyl)cyclopropanol | C5H9BrO | 详情 | 详情 | |
| (XX) | 50287 | 1,5-dibromo-3-pentanone | C5H8Br2O | 详情 | 详情 | |
| (XXI) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |
| (XXII) | 50288 | 2,2-bis(2-bromoethyl)-1,3-dioxolane | C7H12Br2O2 | 详情 | 详情 | |
| (XXIII) | 50289 | C24H27NO4 | 详情 | 详情 | ||
| (XXIV) | 50290 | C22H23NO3 | 详情 | 详情 | ||
| (XXV) | 50291 | C22H25NO3 | 详情 | 详情 | ||
| (XXVI) | 27355 | 4-(2-chloroethyl)morpholine | 3647-69-6 | C6H12ClNO | 详情 | 详情 |
| (XXVII) | 50292 | C28H36N2O4 | 详情 | 详情 | ||
| (XXVIII) | 50293 | C21H30N2O4 | 详情 | 详情 |