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【结 构 式】 
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【分子编号】64952 【品名】(1S)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl 4-chlorobenzenesulfonate 【CA登记号】 |
【 分 子 式 】C16H14ClF3O4S 【 分 子 量 】394.7986696 【元素组成】C 48.68% H 3.57% Cl 8.98% F 14.44% O 16.21% S 8.12% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of the chiral benzyl alcohol (I) with 4-chlorobenzenesulfonyl chloride (II) and DABCO in toluene gives the sulfonate (III), which is condensed with the monoprotected piperazine (IV) by means of K2CO3 in hot toluene/acetonitrile to yield the adduct (V). The deprotection of (V) by means of hot aqueous HCl affords the piperazine derivative (VI), which is condensed with the acyl piperidine (VII) --obtained by condensation of 4,6-dimethylpyrimidine-5-carboxylic acid (VIII) with 4-piperidone (IX) --by means of acetone cyanohydrin or NaCN/AcOH to provide the cyano adduct (X). Finally, this compound is treated with AlMe3 and Me-MgCl in THF/toluene to yield the target compound.
| 【1】 Gala, D.; Leong, W.; Jones, A.D.; Shi, X.; Chen, M.; D'sa, B.A.; Zhu, M.; Xiao, T.; Tang, S.; Goodman, A.J.; Nielsen, C.M.; Lee, G.M.; Gamboa, J.A. (Schering Corp.); Synthesis of piperidine and piperazine cpds. as CCR5 antagonists. WO 0384950 . |
| 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) | 64951 | (1S)-2-methoxy-1-[4-(trifluoromethyl)phenyl]-1-ethanol | C10H11F3O2 | 详情 | 详情 | |
| (II) | 15787 | 4-chlorobenzenesulfonyl chloride;4-chlorobenzene-1-sulfonyl chloride | 98-60-2 | C6H4Cl2O2S | 详情 | 详情 |
| (III) | 64952 | (1S)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl 4-chlorobenzenesulfonate | C16H14ClF3O4S | 详情 | 详情 | |
| (IV) | 50647 | benzyl (3R)-3-methyl-1-piperazinecarboxylate | C13H18N2O2 | 详情 | 详情 | |
| (V) | 64953 | benzyl (3S)-4-{(1R)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl}-3-methyl-1-piperazinecarboxylate | C23H27F3N2O3 | 详情 | 详情 | |
| (VI) | 64946 | 2-methyl-1-{2-(methyloxy)-1-[4-(trifluoromethyl)phenyl]ethyl}piperazine; methyl 2-(2-methyl-1-piperazinyl)-2-[4-(trifluoromethyl)phenyl]ethyl ether | C15H21F3N2O | 详情 | 详情 | |
| (VII) | 64954 | 1-[(4,6-dimethyl-5-pyrimidinyl)carbonyl]-4-piperidinone | C12H15N3O2 | 详情 | 详情 | |
| (VIII) | 64955 | 4,6-dimethyl-5-pyrimidinecarboxylic acid | C7H8N2O2 | 详情 | 详情 | |
| (IX) | 27115 | 4-piperidinone | 40064-34-4 | C5H9NO | 详情 | 详情 |
| (X) | 64956 | 1-[(4,6-dimethyl-5-pyrimidinyl)carbonyl]-4-((3S)-4-{(1R)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl}-3-methylpiperazinyl)-4-piperidinecarbonitrile | C28H35F3N6O2 | 详情 | 详情 |