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【结 构 式】 
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【分子编号】21378 【品名】2-chloro-N-[(1R,2R)-1-hydroxy-7-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl]acetamide 【CA登记号】 |
【 分 子 式 】C13H16ClNO3 【 分 子 量 】269.72768 【元素组成】C 57.89% H 5.98% Cl 13.14% N 5.19% O 17.8% |
合成路线1
该中间体在本合成路线中的序号：(III)1) The acylation of 2-amino-7-methoxy-1-tetralone (I) with chloroacetyl chloride in ethyl acetate - water by means of NaHCO3 gives the corresponding chloroacetamido derivative (II), which is reduced with NaBH4 in ethanol - CHCl3 to trans-2-(chloroacetamido)-7-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol (III). The cyclization of (III) by means of NaH in DMF yields the oxazinone (IV), which is reduced with LiAlH4 in refluxing THF to trans-9-methoxy-3,4,4a,5,6,10b-hexahydro-2H-naphth[1,2-b]-1,4-oxazine (V). The alkylation of (V) with propyl bromide by means of K2CO3 in DMF gives the N-propyl derivative (VI), which is finally demethylated by means of pyridine hydrochloride at 200 C.
| 【1】 Jones, J.H.; McClure, D.E.; Grenda, V.J. (Merck & Co., Inc.); Hexahydronaphth(1,2-b)-1,4-oxazines, process for their preparation and pharmaceutical formulation containing them. EP 0080115 . |
| 【2】 Prous, J.; Castaner, J.; NAXAGOLIDE HYDROCHLORIDE < Prop INNM; USAN >. Drugs Fut 1989, 14, 10, 951. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 | |
| 19502 | Propyl bromide; 1-Bromopropane | 106-94-5 | C3H7Br | 详情 | 详情 | |
| (I) | 21376 | 2-amino-7-methoxy-3,4-dihydro-1(2H)-naphthalenone | C11H13NO2 | 详情 | 详情 | |
| (II) | 21377 | 2-chloro-N-(7-methoxy-1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)acetamide | C13H14ClNO3 | 详情 | 详情 | |
| (III) | 21378 | 2-chloro-N-[(1R,2R)-1-hydroxy-7-methoxy-1,2,3,4-tetrahydro-2-naphthalenyl]acetamide | C13H16ClNO3 | 详情 | 详情 | |
| (IV) | 21379 | (4aR,10bR)-9-methoxy-4a,5,6,10b-tetrahydro-2H-naphtho[1,2-b][1,4]oxazin-3(4H)-one | C13H15NO3 | 详情 | 详情 | |
| (V) | 21380 | (4aR,10bR)-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-yl methyl ether | C13H17NO2 | 详情 | 详情 | |
| (VI) | 21381 | (4aR,10bR)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-yl methyl ether | C16H23NO2 | 详情 | 详情 |