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【结 构 式】 
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【分子编号】38669 【品名】2-chloro-1-phenyl-1-ethanone 【CA登记号】532-27-4 |
【 分 子 式 】C8H7ClO 【 分 子 量 】154.59568 【元素组成】C 62.15% H 4.56% Cl 22.93% O 10.35% |
合成路线1
该中间体在本合成路线中的序号：(IV)The reaction of bromobenzene (I) with 14CO2 by means of Mg in ether gives the corresponding benzoic acid (II), which is treated with SOCl2 and DMAP to yield the benzoyl chloride (III). The homologation of (III) with diazomethane in ether affords the phenacyl chloride (IV), which is enantioselectively reduced with borane and a chiral borolidine catalyst in THF to give (R)-2-chloro-1-phenylethanol (V). The cyclization of (V) by means of NaOH in ethyl ether yields the oxirane (VI), which by reaction with ammonia is converted into the (R)-2-amino-1-phenylethanol (VII). The condensation of (VII) with 4'-chlorobiphenyl-4-carboxylic acid (VIII) by means of CDI in DMF provides the amide (IX), which is cyclized to the oxazoline (X) by means of methanesulfonic anhydride and TEA in THF. Finally, this compound is condensed with imidazole (XI) by heating at 125 C.
| 【1】 Moenius, T.; et al.; C-14 labelling of NVPVID400 - a specific vitamin D-3-hydroxylase inhibitor. J Label Compd Radiopharm 1999, 42, 11, 1053. |
| 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) | 13365 | Monobromobenzene; 1-Bromobenzene；Phenylbromide;bromobenzene | 108-86-1 | C6H5Br | 详情 | 详情 |
| (II) | 10202 | Benzoic acid | 65-85-0 | C7H6O2 | 详情 | 详情 |
| (III) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (IV) | 38669 | 2-chloro-1-phenyl-1-ethanone | 532-27-4 | C8H7ClO | 详情 | 详情 |
| (V) | 38670 | (1R)-2-chloro-1-phenyl-1-ethanol | 1674-30-2 | C8H9ClO | 详情 | 详情 |
| (VI) | 38671 | (2R)-2-phenyloxirane | C8H8O | 详情 | 详情 | |
| (VII) | 10173 | (1R)-2-Amino-1-phenyl-1-ethanol | 2549-14-6 | C8H11NO | 详情 | 详情 |
| (VIII) | 38672 | 4'-chloro[1,1'-biphenyl]-4-carboxylic acid | C13H9ClO2 | 详情 | 详情 | |
| (IX) | 38673 | 4'-chloro-N-[(2R)-2-hydroxy-2-phenylethyl][1,1'-biphenyl]-4-carboxamide | C21H18ClNO2 | 详情 | 详情 | |
| (X) | 38674 | (5S)-2-(4'-chloro[1,1'-biphenyl]-4-yl)-5-phenyl-4,5-dihydro-1,3-oxazole | C21H16ClNO | 详情 | 详情 | |
| (XI) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The title thiazolium salt was prepared by alkylation of 4,5-dimethylthiazole (I) with 2-chloroacetophenone (II) in refluxing acetonitrile.
合成路线3
该中间体在本合成路线中的序号：(XII)2-Amino-6-bromopyridine (II) was prepared by reaction of 2,6-dibromopyridine (I) with ammonium hydroxide in a pressure bomb at 170 C. The amino group of (III) was subsequently blocked as the pyrrole derivative (IV) by condensation with 2,5-hexanedione (III). Diazotization of p-aminophenyl ethanol (V) followed by treatment with KI gave iodo derivative (VI). Subsequent reaction of (VI) with SOCl2 provided chloride (VII). Arylpyridine (VIII) was obtained by lithiation of bromopyridine (IV) with BuLi, followed by conversion to the corresponding organozinc compound with ZnCl2 and palladium-catalyzed coupling with iodide (VII). Pyrrole ring cleavage in (VIII) upon treatment with hydroxylamine furnished aminopyridine (IX). Subsequent condensation with N-Boc-piperazine (X) provided adduct (XI). After acid cleavage of the Boc group of (XI), alkylation of the resulting piperazine with phenacyl chloride (XII) yielded the title compound. Alternatively, the title compound was obtained by condensation of chloride (IX) with N-phenacylpiperazine (XIII).
| 【1】 Qian, W.; Lowe, J.A.; Volkmann, R.A.; et al.; A new class of selective and potent inhibitors of neuronal nitric oxide synthase. Bioorg Med Chem Lett 1999, 9, 17, 2569. |
| 【2】 Lowe, J.A. III; Whittle, P.J. (Pfizer Inc.); 6-Phenylpyridyl-2-amine derivs.. EP 0891332; JP 1999510513; WO 9736871 . |
| 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) | 10159 | 2,6-Dibromopyridine | 626-05-1 | C5H3Br2N | 详情 | 详情 |
| (II) | 41341 | 2-amino-6-bromopyridine; 6-bromo-2-pyridinamine; 6-bromo-2-pyridinylamine | 19798-81-3 | C5H5BrN2 | 详情 | 详情 |
| (III) | 24848 | acetonyl acetone;1,2-Diacetylethane;a,b-Diacetylethane;2,5-Diketohexane;Diacetonyl;Acetonylacetone;2,5-Dioxohexane;2,5-hexanedione | 110-13-4 | C6H10O2 | 详情 | 详情 |
| (IV) | 41342 | 2-bromo-6-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine | C11H11BrN2 | 详情 | 详情 | |
| (V) | 14019 | p-Aminophenylethanol; 2-(4-Aminophenyl)-1-ethanol | 104-10-9 | C8H11NO | 详情 | 详情 |
| (VI) | 30973 | 2-(4-iodophenyl)-1-ethanol | C8H9IO | 详情 | 详情 | |
| (VII) | 41343 | 1-(2-chloroethyl)-4-iodobenzene | C8H8ClI | 详情 | 详情 | |
| (VIII) | 41344 | 2-[4-(2-chloroethyl)phenyl]-6-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine | C19H19ClN2 | 详情 | 详情 | |
| (IX) | 41345 | 6-[4-(2-chloroethyl)phenyl]-2-pyridinamine; 6-[4-(2-chloroethyl)phenyl]-2-pyridinylamine | C13H13ClN2 | 详情 | 详情 | |
| (X) | 13225 | N-tert-Butoxycarbonyl piperazine; tert-butyl 1-piperazinecarboxylate;tert-butyl piperazine-1-carboxylate | 143238-38-4 | C9H18N2O2 | 详情 | 详情 |
| (XI) | 41346 | tert-butyl 4-[4-(6-amino-2-pyridinyl)phenethyl]-1-piperazinecarboxylate | C22H30N4O2 | 详情 | 详情 | |
| (XII) | 38669 | 2-chloro-1-phenyl-1-ethanone | 532-27-4 | C8H7ClO | 详情 | 详情 |
| (XIII) | 41347 | 1-phenyl-2-(1-piperazinyl)-1-ethanone | C12H16N2O | 详情 | 详情 |