【结 构 式】 |
【分子编号】28145 【品名】2-(aminomethyl)-1-phenylcyclopropanecarboxylic acid 【CA登记号】 |
【 分 子 式 】C11H13NO2 【 分 子 量 】191.22976 【元素组成】C 69.09% H 6.85% N 7.32% O 16.73% |
合成路线1
该中间体在本合成路线中的序号:(II)This compound can be prepared in several ways from the lactone (I), which is obtained by treatment of benzyl cyanide (A) and epichlorhydrin (B) with sodium amide: 1) The opening of lactone (I) with SOBr2-ethanol gives a bromo ester, which is treated successively by ammonia and sodium hydroxide to yield the amino acid (II). The reaction of (II) with SOCl2 and diethylamine in ethanol gives the final product, which is converted to the hydrochloric salt by treatment with HCl ethanol. 2) Lactone (I), opened with 33% HBr-AcOH, gives the bromo acid (III), which is treated by SOCl2 and then diethylamine in ethanol. The bromoamide (IV) reacts with potassium phthalimide and is deprotected by hydrazine or methylamine to yield, after salification, title compound. 3) Lactone (I) is treated by potassium phthalimide and then SOCl2 and diethylamine in EtOH to give compound (V), treated as above. 4) Bromoamide (IV) can be treated by hexamethylenetetramine in butanol and hydrolyzed by refluxing with 15% HCl in ethanol.
【1】 Kasama, S.; et al.; Synthesis 1978, 4, 10, 304. |
【2】 Patoiseau, J.-F.; Mouzin, G.; Bonnaud, B.; Cousse, H. (Pierre Fabre Medicament); Process for the preparation of (Z)-1-phenyl-1-diethylaminocarbonyl-2-aminomethyl-cyclopropane. EP 0200638; FR 2581059 . |
【3】 Cousse, H.; Hascoet, P. (Pierre Fabre Medicament); Industrial process for the production of midalcipran. FR 2581060 . |
【4】 Mouzin, G.; Cousse, H.; Bonnaud, B.; Morre, M.; Stenger, A. (Pierre Fabre Médicament); 1-Aryl-2-aminomethyl cyclopropane carboxyamide (Z) deivatives and their use as useful drugs in the treatment of disturbances of the central nervous system. EP 0068999; FR 2508035; JP 58004752; US 4478836 . |
【5】 Briley, M.; Midalcipran Hydrochloride. Drugs Fut 1986, 11, 1, 21. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(B) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
(A) | 17046 | Phenylacetonitrile; 2-phenylacetonitrile; Benzyl cyanide | 140-29-4 | C8H7N | 详情 | 详情 |
(F) | 27890 | Potassium phthalimide | 1074-82-4 | C8H4KNO2 | 详情 | 详情 |
(G) | 28148 | 1-([2-[(diethylamino)carbonyl]-2-phenylcyclopropyl]methyl)-3,5,7-triaza-1-azoniatricyclo[3.3.1.1(3,7)]decane | C21H32N5O | 详情 | 详情 | |
(E) | 28150 | 2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1-phenylcyclopropanecarboxylic acid | C19H15NO4 | 详情 | 详情 | |
(D) | 28151 | 2-(hydroxymethyl)-1-phenylcyclopropanecarboxylic acid | C11H12O3 | 详情 | 详情 | |
(I) | 28144 | 1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one | C11H10O2 | 详情 | 详情 | |
(II) | 28145 | 2-(aminomethyl)-1-phenylcyclopropanecarboxylic acid | C11H13NO2 | 详情 | 详情 | |
(III) | 28146 | 2-(bromomethyl)-1-phenylcyclopropanecarboxylic acid | C11H11BrO2 | 详情 | 详情 | |
(IV) | 28147 | 2-(bromomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide | C15H20BrNO | 详情 | 详情 | |
(V) | 28149 | 2-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-N,N-diethyl-1-phenylcyclopropanecarboxamide | C23H24N2O3 | 详情 | 详情 | |
(C) | 28143 | 2-(hydroxymethyl)-1-phenylcyclopropanecarboxylic acid | C11H12O3 | 详情 | 详情 |