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【结 构 式】 
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【分子编号】64784 【品名】ethyl 2-[2,3-dihydro-1,4-benzodioxin-5-yl(2-ethoxy-2-oxoethyl)amino]acetate 【CA登记号】 |
【 分 子 式 】C16H21NO6 【 分 子 量 】323.34588 【元素组成】C 59.43% H 6.55% N 4.33% O 29.69% |
合成路线1
该中间体在本合成路线中的序号：(IV)The reaction of 4-aminobenzoic acid ethyl ester (I) with acryloyl chloride (II) by means of TEA in dichloromethane gives the corresponding acrylamide (III), which is condensed with 4,5,6,7-tetrahydro-1H-indol-4-one (IV) by means of K2CO3 in hot DMF to yield NEO-339. (1,2)
| 【1】 Mohan, P.; Fick, D.B.; McKinley, L.K.; Prigaro, B.J.; Pfadenhauer, E.; Helton, D.; Search, design and discovery of NEO-339, a novel agent that increases attentional processes associated with cognition. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 249. |
| 【2】 Foreman, M.M.; Glasky, A.J.; Fick, D.B. (Spectrum Pharmaceuticals, Inc.); Synthesis and methods of use of tetrahydroisoindolone analogues and derivs.. EP 1383742; WO 0285856 . |
| 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) | 16498 | Benzocaine; ethyl 4-aminobenzoate | 94-09-7 | C9H11NO2 | 详情 | 详情 |
| (II) | 11577 | Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride | 814-68-6 | C3H3ClO | 详情 | 详情 |
| (III) | 64783 | ethyl 4-(acryloylamino)benzoate | C12H13NO3 | 详情 | 详情 | |
| (IV) | 64784 | ethyl 2-[2,3-dihydro-1,4-benzodioxin-5-yl(2-ethoxy-2-oxoethyl)amino]acetate | C16H21NO6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)The intermediate dimesylate (VI) can be obtained as follows: The condensation of 2,3-dihydro-1,4-benzodioxin-5-amine (I) with ethyl bromoacetate (II) by means of Hunig's base and NaI in refluxing toluene gives the tertiary amine (III), which is reduced by means of LiAlH4 in THF to yield the diethanolamine (IV). Finally, this compound is esterified by means of mesyl chloride (V) to provide the desired dimesylate intermediate (VI). Alternatively, the diethanolamine (IV) can be obtained by direct condensation of 2,3-dihydro-1,4-benzodioxin-5-amine (I) with 2-chloroethanol (VII) by means of Hunig's base.
| 【1】 Jirkovsky, I.; Zeldis, J.; Chan, A.W.-Y.; Fiegelson, G.B. (Wyeth); Preparation of N1-(2'-pyridyl)-1,2-propanediamine sulfamic acid and its use in the synthesis of biologically active piperazines. WO 0378396 . |
| 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) | 22000 | 2,3-dihydro-1,4-benzodioxin-5-amine; 2,3-dihydro-1,4-benzodioxin-5-ylamine; 5-Amino-1,4-benzodioxane | 16081-46-2 | C8H9NO2 | 详情 | 详情 |
| (II) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (III) | 64784 | ethyl 2-[2,3-dihydro-1,4-benzodioxin-5-yl(2-ethoxy-2-oxoethyl)amino]acetate | C16H21NO6 | 详情 | 详情 | |
| (IV) | 64785 | 2-[2,3-dihydro-1,4-benzodioxin-5-yl(2-hydroxyethyl)amino]-1-ethanol | C12H17NO4 | 详情 | 详情 | |
| (V) | 13467 | Methanesulfonyl chloride;Mesyl chloride;Methylsulfonyl chloride;Methanesulfonic acid chloride;Methanesulfonyl chloride;Methanesulphonyl chloride | 124-63-0 | CH3ClO2S | 详情 | 详情 |
| (VI) | 64786 | 2-(2,3-dihydro-1,4-benzodioxin-5-yl{2-[(methylsulfonyl)oxy]ethyl}amino)ethyl methanesulfonate | C14H21NO8S2 | 详情 | 详情 | |
| (VII) | 10384 | 2-Chloro-1-ethanol; Ethylene chlorohydrin | 107-07-3 | C2H5ClO | 详情 | 详情 |