|
【结 构 式】 
|
【分子编号】50285 【品名】3-Bromopropionic acid methyl ester; Methyl 3-bromopropionate 【CA登记号】3395-91-3 |
【 分 子 式 】C4H7BrO2 【 分 子 量 】167.00238 【元素组成】C 28.77% H 4.22% Br 47.85% O 19.16% |
合成路线1
该中间体在本合成路线中的序号：(XVII)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 |
合成路线2
该中间体在本合成路线中的序号：(V)Acylation of Meldrum's acid (I) with 3-tryphenylmethylsulfanyl)propionic acid (II) by means of DCC produces the intermediate adduct (III), which is subsequently reduced to the tritylsulfanyl derivative (IV) by using NaBH4/AcOH. Alkylation of (IV) with methyl 3-bromopropionate (V) in the presence of NaOMe provides the 5,5-disubstituted dioxanedione (VI). Basic hydrolysis of (VI) gives rise to the tricarboxylic acid (VII), which is further decarboxylated to (VIII) in hot DMSO. Finally the S-trityl protecting gropu is removed by treatment with trifluoroacetic acid and triisopropylsilane.
| 【1】 Jackson, P.F.; Slusher, B.S.; Majer, P.; Maclin, K.M.; Wang, E.; Lapidus, R.S. (Guilford Pharmaceuticals Inc.); NAALADase inhibitors useful as pharmaceutical cpds. and compsns.. JP 2002519408; US 6395718; WO 0001668 . |
| 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) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (II) | 63154 | 3-[(triphenylmethyl)sulfanyl]propanoic acid | C22H20O2S | 详情 | 详情 | |
| (III) | 63155 | 5-{1-hydroxy-3-[(triphenylmethyl)sulfanyl]propylidene}-2,2-dimethyl-1,3-dioxane-4,6-dione | C28H26O5S | 详情 | 详情 | |
| (IV) | 63156 | 2,2-dimethyl-5-{3-[(triphenylmethyl)sulfanyl]propyl}-1,3-dioxane-4,6-dione | C28H28O4S | 详情 | 详情 | |
| (V) | 50285 | 3-Bromopropionic acid methyl ester; Methyl 3-bromopropionate | 3395-91-3 | C4H7BrO2 | 详情 | 详情 |
| (VI) | 63157 | methyl 3-(2,2-dimethyl-4,6-dioxo-5-{3-[(triphenylmethyl)sulfanyl]propyl}-1,3-dioxan-5-yl)propanoate | C32H34O6S | 详情 | 详情 | |
| (VII) | 63158 | 6-[(triphenylmethyl)sulfanyl]-1,3,3-hexanetricarboxylic acid | C28H28O6S | 详情 | 详情 | |
| (VIII) | 63159 | 2-{3-[(triphenylmethyl)sulfanyl]propyl}pentanedioic acid | C27H28O4S | 详情 | 详情 |