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【结 构 式】 
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【分子编号】32278 【品名】ethyl 2-aminobenzoate 【CA登记号】87-25-2 |
【 分 子 式 】C9H11NO2 【 分 子 量 】165.19188 【元素组成】C 65.44% H 6.71% N 8.48% O 19.37% |
合成路线1
该中间体在本合成路线中的序号：(VII)By reaction of 4-(p-fluorobenzoyl)piperidine (I) with 3-(2-chloroethyl)-2,4-(1H,3H)-quinazolinedione (II) by means of Na2CO3 in refluxing 4-methyl-2-pentanone. The starting compounds are prepared as follows: 1) The Grignard reaction of N-benzyl-4-cyanopiperidine (III) with p-fluorophenylmagnesium bromide (IV) ethyl ether gives N-benzyl-4-p-fluorobenzoyl)piperidine (V), which by reaction with Na2CO3 and ethyl chloroformate (A) is converted into N-ethoxycarbonyl-4-(p-fluorobenzoyl)piperidine (VI). Finally, this compound is hydrolyzed with 48% HBr to give (I). 2) The reaction of ethyl anthranilate (VII) with ethyl chloroformate (A) in refluxing xylene gives ethyl 2-(ethoxycarbonylamino)benzoate (VIII), which is cyclized with 2-aminoethanol (B) at 170 C to afford 3-(2-hydroxyethyl)-2,4-(1H,3H)-quinazolinedione (IX). Finally, this compound is treated with SOCl2 in refluxing chloroform to afford (II).
| 【1】 Van Der, M.; Keninis, L.; Vandenberk, J.; Van Heertum, A. (Janssen Pharmaceutica NV); Piperidinylalkyl quinazoline compounds, composition and method of use. EP 0013612; JP 55105679; US 4335127 . |
| 【2】 Blancafort, P.; Paton, D.M.; Serradell, M.N.; Castaner, J.; Ketanserin. Drugs Fut 1981, 6, 11, 684. |
| 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) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
| (B) | 11229 | 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate | 541-41-3 | C3H5ClO2 | 详情 | 详情 |
| (I) | 21497 | (4-Fluorophenyl)(4-piperidinyl)methanone; 4-(4-Fluorobenzoyl)piperidine; 4-(p-Fluorobenzoyl)piperidine | 56346-57-7 | C12H14FNO | 详情 | 详情 |
| (II) | 32277 | 3-(2-chloroethyl)-2,4(1H,3H)-quinazolinedione | 5081-87-8 | C10H9ClN2O2 | 详情 | 详情 |
| (III) | 29013 | 1-benzyl-4-piperidinecarbonitrile | C13H16N2 | 详情 | 详情 | |
| (IV) | 13643 | 4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide | 352-13-6 | C6H4BrFMg | 详情 | 详情 |
| (V) | 29014 | (1-benzyl-4-piperidinyl)(4-fluorophenyl)methanone | C19H20FNO | 详情 | 详情 | |
| (VI) | 29015 | ethyl 4-(4-fluorobenzoyl)-1-piperidinecarboxylate | C15H18FNO3 | 详情 | 详情 | |
| (VII) | 32278 | ethyl 2-aminobenzoate | 87-25-2 | C9H11NO2 | 详情 | 详情 |
| (VIII) | 32279 | ethyl 2-[(ethoxycarbonyl)amino]benzoate | C12H15NO4 | 详情 | 详情 | |
| (IX) | 32280 | 3-(2-hydroxyethyl)-2,4(1H,3H)-quinazolinedione | C10H10N2O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)
| 【1】 Masagaki T, Kakita T, et aL 2001. Preparation of antiallergic epinatine and imidazoline compounds as their intermediates. JP 2001064282 |
| 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) | 32278 | ethyl 2-aminobenzoate | 87-25-2 | C9H11NO2 | 详情 | 详情 |
| (II) | 66334 | ethyl 2-((2-amino-1-phenylethyl)amino)benzoate | C17H20N2O2 | 详情 | 详情 | |
| (III) | 66335 | (2-((2-amino-1-phenylethyl)amino)phenyl)methanol | C15H18N2O | 详情 | 详情 | |
| (IV) | 66336 | N-((2-((2-(hydroxymethyl)phenyl)amino)-2-phenylethyl)carbamoyl)benzamide | C23H23N3O3 | 详情 | 详情 | |
| (V) | 66337 | N-(1-(2-(hydroxymethyl)phenyl)-5-phenyl-4,5-dihydro-1H-imidazol-2-yl)benzamide | C23H21N3O2 | 详情 | 详情 | |
| (VI) | 23530 | benzoyl isothiocyanate | 532-55-8 | C8H5NOS | 详情 | 详情 |