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【结 构 式】 
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【分子编号】44195 【品名】5-(hydroxymethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one 【CA登记号】 |
【 分 子 式 】C3H5N3O2 【 分 子 量 】115.09172 【元素组成】C 31.31% H 4.38% N 36.51% O 27.8% |
合成路线1
该中间体在本合成路线中的序号：(XXXII)Synthesis of 250157: Alternatively, the final compound can be obtained by direct condensation of (VI) with chlorotriazolinone (XXVI) in DMF/H2O in the presence of K2CO3 or DIEA. For the obtention of (XXVI), two routes can be followed: 1. Reaction of semicarbazide (XXVII) with orthoester (XXVIII) in MeOH; and 2. Condensation of semicarbazide (XXVII) with benzyloxyacetyl chloride (XXIX) in THF/H2O in the presence of NaOH to provide adduct (XXX), which is then cyclized by means of refluxing NaOH to afford triazolinone (XXXI). Debenzylation of (XXXI) by hydrogenation over Pd/C in MeOH/H2O yields alcohol (XXXII), which is finally treated with thionyl chloride.
| 【1】 Castaner, J.; Silvestre, J.S.; Bayes, M.; Sorbera, L.A.; Aprepitant and L-758298. Drugs Fut 2002, 27, 3, 211. |
| 【2】 Cowden, C.J.; et al.; A new synthesis of 1,2,4-triazolin-5-ones: Application to the convergent synthesis of an NK1 antagonist. Tetrahedron Lett 2000, 41, 44, 8661. |
| 【3】 Cowden, C.J. (Merck Sharp & Dohme Ltd.); Process for the preparation of 1,2,4-triazolin-5-one derivs.. WO 0196315 . |
| 【4】 Dolling, U.H.; Wilson, R.D.; Hands, D.; Cottrell, I.F. (Merck Sharp & Dohme Ltd.); Chemical synthesis of morpholine derivs.. WO 9965900 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 18293 | (1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl (2R,3S)-3-(4-fluorophenyl)morpholinyl ether; (2R,3S)-2-([(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]oxy)-3-(4-fluorophenyl)morpholine | 171482-05-6 | C20H18F7NO2 | 详情 | 详情 |
| (XXVI) | 44196 | 5-(chloromethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one | C3H4ClN3O | 详情 | 详情 | |
| (XXVII) | 23944 | 1-Hydrazinecarboxamide | 563-41-7 | CH5N3O | 详情 | 详情 |
| (XXVIII) | 44197 | 2-chloro-1,1-dimethoxyethyl methyl ether; 2-chloro-1,1,1-trimethoxyethane | C5H11ClO3 | 详情 | 详情 | |
| (XXIX) | 10493 | 2-(Benzyloxy)acetyl chloride; Benzyloxyacetyl chloride | 19810-31-2 | C9H9ClO2 | 详情 | 详情 |
| (XXX) | 44193 | 2-[2-(benzyloxy)acetyl]-1-hydrazinecarboxamide | C10H13N3O3 | 详情 | 详情 | |
| (XXXI) | 44194 | 5-[(benzyloxy)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one | C10H11N3O2 | 详情 | 详情 | |
| (XXXII) | 44195 | 5-(hydroxymethyl)-2,4-dihydro-3H-1,2,4-triazol-3-one | C3H5N3O2 | 详情 | 详情 |