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【结 构 式】 
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【分子编号】42115 【品名】(5R)-1-(3-chlorophenyl)-5-[(ethylsulfonyl)methyl]-2-piperazinone 【CA登记号】 |
【 分 子 式 】C13H17ClN2O3S 【 分 子 量 】316.80836 【元素组成】C 49.29% H 5.41% Cl 11.19% N 8.84% O 15.15% S 10.12% |
合成路线1
该中间体在本合成路线中的序号：(IX)The reductive alkylation of 3-chloroaniline (I) with L-S-trityl-N-Boc-cysteinal (II) in the presence of sodium triacetoxyborohydride produced amine (III). Chloroacetylation of (III) followed by cesium carbonate-induced cyclization of the resulting chloroacetamide (IV) furnished the protected piperazinone (V). The S-trityl group of (V) was deprotected by treatment with silver nitrate and pyridine, yielding thiol (VI), which was subsequently alkylated with ethyl iodide to give thioether (VII). Sulfur oxidation by means of magnesium monoperoxyphthalate in methanol afforded sulfone (VIII). Then, acid deprotection of the Boc protecting group of (VIII) provided the intermediate piperazinone (IX).
| 【1】 Anthony, N.J.; Ciccarone, T.M.; Gomez, R.P.; Hutchinson, J.H.; Williams, T.M.; Dinsmore, C.J.; Stokker, G.E. (Merck & Co., Inc.); Inhibitors of farnesyl-protein transferase. EP 0820445; JP 1998511098; US 5856326; WO 9630343 . |
| 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) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (II) | 17953 | tert-butyl (1R)-1-formyl-2-(tritylsulfanyl)ethylcarbamate | C27H29NO3S | 详情 | 详情 | |
| (III) | 42109 | tert-butyl (1R)-2-(3-chloroanilino)-1-[(tritylsulfanyl)methyl]ethylcarbamate | C33H35ClN2O2S | 详情 | 详情 | |
| (IV) | 42110 | tert-butyl (1R)-2-[3-chloro(2-chloroacetyl)anilino]-1-[(tritylsulfanyl)methyl]ethylcarbamate | C35H36Cl2N2O3S | 详情 | 详情 | |
| (V) | 42111 | tert-butyl (2R)-4-(3-chlorophenyl)-5-oxo-2-[(tritylsulfanyl)methyl]-1-piperazinecarboxylate | C35H35ClN2O3S | 详情 | 详情 | |
| (VI) | 42112 | tert-butyl (2R)-4-(3-chlorophenyl)-5-oxo-2-(sulfanylmethyl)-1-piperazinecarboxylate | C16H21ClN2O3S | 详情 | 详情 | |
| (VII) | 42113 | tert-butyl (2R)-4-(3-chlorophenyl)-2-[(ethylsulfanyl)methyl]-5-oxo-1-piperazinecarboxylate | C18H25ClN2O3S | 详情 | 详情 | |
| (VIII) | 42114 | tert-butyl (2R)-4-(3-chlorophenyl)-2-[(ethylsulfonyl)methyl]-5-oxo-1-piperazinecarboxylate | C18H25ClN2O5S | 详情 | 详情 | |
| (IX) | 42115 | (5R)-1-(3-chlorophenyl)-5-[(ethylsulfonyl)methyl]-2-piperazinone | C13H17ClN2O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)The regioselective protection of 4-hydroxymethylimidazole (X) with trityl chloride gave the 1-trityl imidazole (XI), which was further acetylated to afford acetate (XII). Alkylation of imidazole (XII) with 4-cyanobenzyl bromide (XIII), followed by solvolysis of the resulting imidazolium salt in refluxing methanol, produced the cyanobenzyl imidazole (XIV). Acetate hydrolysis and subsequent oxidation of alcohol (XV) furnished aldehyde (XVI). The title compound was obtained by reductive alkylation of piperazinone (IX) with aldehyde (XVI) in the presence of sodium triacetoxyborohydride.
| 【1】 Anthony, N.J.; Ciccarone, T.M.; Gomez, R.P.; Hutchinson, J.H.; Williams, T.M.; Dinsmore, C.J.; Stokker, G.E. (Merck & Co., Inc.); Inhibitors of farnesyl-protein transferase. EP 0820445; JP 1998511098; US 5856326; WO 9630343 . |
| 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) | 42115 | (5R)-1-(3-chlorophenyl)-5-[(ethylsulfonyl)methyl]-2-piperazinone | C13H17ClN2O3S | 详情 | 详情 | |
| (X) | 42116 | 1H-imidazol-5-ylmethanol | C4H6N2O | 详情 | 详情 | |
| (XI) | 38392 | (1-trityl-1H-imidazol-4-yl)methanol | C23H20N2O | 详情 | 详情 | |
| (XII) | 38391 | (1-trityl-1H-imidazol-4-yl)methyl acetate | C25H22N2O2 | 详情 | 详情 | |
| (XIII) | 14200 | 4-(Bromomethyl)benzonitrile; alpha-Bromo-p-tolunitrile | 17201-43-3 | C8H6BrN | 详情 | 详情 |
| (XIV) | 38390 | [1-(4-cyanobenzyl)-1H-imidazol-5-yl]methyl acetate | C14H13N3O2 | 详情 | 详情 | |
| (XV) | 38389 | 4-[[5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]benzonitrile | C12H11N3O | 详情 | 详情 | |
| (XVI) | 39388 | C54H67N11O13S3 | 详情 | 详情 |