【结 构 式】 |
【药物名称】 【化学名称】2-(4-Ethoxy-3-thienyloxymethyl)morpholine 【CA登记号】 【 分 子 式 】C11H17NO3S 【 分 子 量 】243.32704 |
【开发单位】CSIC (Originator), Universidad de La Laguna (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS |
合成路线1
Condensation of epoxy derivative (I) with 1,2,3-oxathiazolidine-2,2-dioxide (II) in the presence of NaOH in aqueous DMSO directly afforded the target morpholine.
【1】 Corral, C.; Lissavetzky, J.; Sánchez-Mateo, C.C.; Darias, V.; Expósito-Orta, M.A.; Martín-Conde, J.A.; Manzanares, I.; Synthesis and preliminary pharmacological evaluation of thiophene analogues of viloxazine as potential antidepressant drugs. Bioorg Med Chem 1999, 7, 7, 1349. |
合成路线2
In an alternative method, ring opening of epoxide (I) with benzylamine produced aminoalcohol (III). Subsequent coupling of (III) with chloroacetyl chloride (IV) yielded chloroacetamide (V), which was cyclized to the morpholinone (VI) upon treatment with NaOMe in MeOH. Reduction of the lactam function of (VI) with LiAlH4 gave the N-benzyl morpholine (VII). Finally, the N-benzyl group of (VII) was cleaved by hydrogenolysis using Pearlman's catalyst.
【1】 Corral, C.; Lissavetzky, J.; Sánchez-Mateo, C.C.; Darias, V.; Expósito-Orta, M.A.; Martín-Conde, J.A.; Manzanares, I.; Synthesis and preliminary pharmacological evaluation of thiophene analogues of viloxazine as potential antidepressant drugs. Bioorg Med Chem 1999, 7, 7, 1349. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 | |
(I) | 34727 | 4-ethoxy-3-thienyl 2-oxiranylmethyl ether; 2-[[(4-ethoxy-3-thienyl)oxy]methyl]oxirane | C9H12O3S | 详情 | 详情 | |
(III) | 34729 | 1-(benzylamino)-3-[(4-ethoxy-3-thienyl)oxy]-2-propanol | C16H21NO3S | 详情 | 详情 | |
(IV) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
(V) | 34730 | N-benzyl-2-chloro-N-[3-[(4-ethoxy-3-thienyl)oxy]-2-hydroxypropyl]acetamide | C18H22ClNO4S | 详情 | 详情 | |
(VI) | 34731 | 4-benzyl-6-[[(4-ethoxy-3-thienyl)oxy]methyl]-3-morpholinone | C18H21NO4S | 详情 | 详情 | |
(VII) | 34732 | 4-benzyl-2-[[(4-ethoxy-3-thienyl)oxy]methyl]morpholine; 4-[(4-benzyl-2-morpholinyl)methoxy]-3-thienyl ethyl ether | C18H23NO3S | 详情 | 详情 |