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【结 构 式】 
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【分子编号】35607 【品名】tert-butyl (1S)-1-([[4,4-bis(4-fluorophenyl)butyl]amino]carbonyl)-3-methylbutyl(methyl)carbamate 【CA登记号】 |
【 分 子 式 】C28H38F2N2O3 【 分 子 量 】488.6182064 【元素组成】C 68.83% H 7.84% F 7.78% N 5.73% O 9.82% |
合成路线1
该中间体在本合成路线中的序号：(VI)Condensation of 4,4-bis(4-fluorophenyl)butyl bromide (I) with potassium phthalimide (II) in hot DMF yielded the substituted phthalimide (III). Deprotection of the phthalimido group of (III) to give primary amine (IV) was effected by treatment with NaBH4, followed by methanolic HCl. Subsequent coupling of (IV) with N-Boc-N-methyl-L-leucine (V) by means of O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate furnished amide (VI). Finally, the Boc group of (VI) was deprotected using trifluoroacetic acid in CH2Cl2 and treated with HCl.
| 【1】 Song, Y.; Connor, D.T.; Bowersox, S.S.; et al.; (S)-4-methyl-2-(methylamino)pentanoic acid [4,4-bis(4-fluorophenyl)butyl]amide hydrochloride, a novel calcium channel antagonist, is efficacious in several animal models of pain. J Med Chem 2000, 43, 19, 3474. |
| 【2】 Song, Y.; Rafferty, M.F.; Ryder, T.R.; Sercel, A.D.; Connor, D.T.; Malone, T.C.; Hu, L.-Y.; Roth, B.D. (Pfizer Inc.); Substd. diarylalkyl amides as calcium channel antagonists. WO 9955688 . |
| 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) | 35603 | 1-[4-bromo-1-(4-fluorophenyl)butyl]-4-fluorobenzene | C16H15BrF2 | 详情 | 详情 | |
| (II) | 27890 | Potassium phthalimide | 1074-82-4 | C8H4KNO2 | 详情 | 详情 |
| (III) | 35604 | 2-[4,4-bis(4-fluorophenyl)butyl]-1H-isoindole-1,3(2H)-dione | C24H19F2NO2 | 详情 | 详情 | |
| (IV) | 35605 | 4,4-bis(4-fluorophenyl)-1-butanamine; 4,4-bis(4-fluorophenyl)butylamine | C16H17F2N | 详情 | 详情 | |
| (V) | 26295 | (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-4-methylpentanoic acid | 609-23-4 | C12H23NO4 | 详情 | 详情 |
| (VI) | 35607 | tert-butyl (1S)-1-([[4,4-bis(4-fluorophenyl)butyl]amino]carbonyl)-3-methylbutyl(methyl)carbamate | C28H38F2N2O3 | 详情 | 详情 |