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【结 构 式】 
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【分子编号】43327 【品名】1-benzyl-4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine 【CA登记号】 |
【 分 子 式 】C18H18FN 【 分 子 量 】267.3460632 【元素组成】C 80.87% H 6.79% F 7.11% N 5.24% |
合成路线1
该中间体在本合成路线中的序号：(XV)Addition of 4-fluorophenylmagnesium bromide (XIII) to 1-benzyl-4-piperidinone (XII) afforded carbinol (XIV), which was dehydrated to the tetrahydropyridine (XV) by treatment with p-toluenesulfonic acid in refluxing toluene. Hydrogenation of the olefin (XV) with concomitant benzyl group hydrogenolysis gave 4-(4-fluorophenyl)piperidine (XVI) (1). This compound was also obtained by catalytic hydrogenation of the commercially available 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (XVII). Alkylation of piperidine (XVI) with N-(3-bromopropyl)phthalimide (XVIII) provided adduct (XIX), which was subjected to hydrazinolysis in refluxing MeOH to furnish the primary amine (XX). Deprotonation of oxazolidine (IX) with n-butyllithium in THF at -78 C, followed by condensation with p-nitrophenyl chloroformate, gave the p-nitrophenoxycarbonyl derivative (XXI). This was finally coupled with amine (XX) to furnish the title carboxamide.
| 【1】 Tian, D.; Jeon, Y.; Lagu, B.; et al.; De novo design of a novel oxazolidinone analogue as a potent and selective alpha1A adrenergic receptor antagonist with high oral bioavailability. J Med Chem 2000, 43, 15, 2775. |
| 【2】 Broten, T.P.; Nichtberger, S.A.; Siegl, P.K.S. (Merck & Co., Inc.); Combination therapy for the treatment of benign prostatic hyperplasia. WO 9948530 . |
| 【3】 Marzabadi, M.R.; Wong, W.C.; Gluchowski, C.; Tian, D.; Nagarathnam, D.; Lagu, B.; Dhar, T.G.M.; Jeon, Y.T. (Synaptic Pharmaceutical Corp.); Heterocyclic substd. piperidines and uses thereof. EP 0988295; WO 9857940 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 43324 | (4S,5S)-4-(3,4-difluorophenyl)-5-methyl-1,3-oxazolidin-2-one | C10H9F2NO2 | 详情 | 详情 | |
| (XII) | 15720 | 1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one | 3612-20-2 | C12H15NO | 详情 | 详情 |
| (XIII) | 13643 | 4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide | 352-13-6 | C6H4BrFMg | 详情 | 详情 |
| (XIV) | 15722 | 1-benzyl-4-(4-fluorophenyl)-4-piperidinol | C18H20FNO | 详情 | 详情 | |
| (XV) | 43327 | 1-benzyl-4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine | C18H18FN | 详情 | 详情 | |
| (XVI) | 39299 | 4-(4-fluorophenyl)piperidine | 37656-48-7 | C11H14FN | 详情 | 详情 |
| (XVII) | 23465 | 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine | 1978-59-2 | C11H12FN | 详情 | 详情 |
| (XVIII) | 15216 | N-(3-Bromopropyl)phthalimide; 2-(3-bromopropyl)-1H-isoindole-1,3(2H)-dione | 5460-29-7 | C11H10BrNO2 | 详情 | 详情 |
| (XIX) | 39300 | 2-[3-[4-(4-fluorophenyl)-1-piperidinyl]propyl]-1H-isoindole-1,3(2H)-dione | C22H23FN2O2 | 详情 | 详情 | |
| (XX) | 39302 | 3-[4-(4-fluorophenyl)-1-piperidinyl]propylamine; 3-[4-(4-fluorophenyl)-1-piperidinyl]-1-propanamine | C14H21FN2 | 详情 | 详情 | |
| (XXI) | 43328 | 4-nitrophenyl (4S,5S)-4-(3,4-difluorophenyl)-5-methyl-2-oxo-1,3-oxazolidine-3-carboxylate | C17H12F2N2O6 | 详情 | 详情 |