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【结 构 式】 
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【分子编号】11413 【品名】1-(2-Naphthyl)-1-ethanone; Methyl 2-naphthyl ketone 【CA登记号】93-08-3 |
【 分 子 式 】C12H10O 【 分 子 量 】170.2108 【元素组成】C 84.68% H 5.92% O 9.4% |
合成路线1
该中间体在本合成路线中的序号：(II)A new enantioselective synthesis of SK&F-104353 has been reported: The compound can be prepared in two related ways: 1) The condensation of 2-(8-phenyloctyl)benzaldehyde (I) with 2'-acetonaphthone (II) by means of NaOEt in ethanol gives (E)-1-(2-naphthyl)-3-[2-(8-phenyloctyl)phenyl]-2-propen-1-one (III), which is regioselectively epoxidized with H2O2 and poly-L-leucine in hexane/water to yield the corresponding (2R-trans)-epoxide (IV). The oxidation of (IV) with m-chloroperbenzoic acid in CH2Cl2 affords (2R-trans)-3-[2-(8-phenyloctyl)phenyl]oxirane-2-carboxylic acid 2-naphthyl ester (V), which is hydrolyzed with LiOH in ethanol to the corresponding lithium salt (VI). Finally, (VI) is condensed with 3-mercaptopropionic acid methyl ester (VII) by means of NaOMe in methanol to give a mixture of regioisomers that are separated by column chromatography. 2) The reaction of the oxiranyl ester (V) with ammonia in acetone/water yields the corresponding amide (VIII), which is condensed with the sodium salt of propenoate (VII) by means of titanium tetrapropoxide in CH2Cl2 to afford the amide ester (X). The basic hydrolysis of (X) with NaOH in methanol gives the corresponding acid amide (XI), which is finally submitted to acid hydrolysis with aqueous HCl.
| 【1】 Flisak, J.R.; Lantos, I.; Snyder, L.; Gombatz, K.J.; Mendelson, W.L.; Jarmas, A.A.; Holmes, M.M.; Remich, J.J.; Novack, V.J.; A practical, enantioselective synthesis of SK&F 104353. J Org Chem 1993, 58, 23, 6247. |
| 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) | 11408 | 2-(8-Phenyloctyl)benzaldehyde | C21H26O | 详情 | 详情 | |
| (II) | 11413 | 1-(2-Naphthyl)-1-ethanone; Methyl 2-naphthyl ketone | 93-08-3 | C12H10O | 详情 | 详情 |
| (III) | 11414 | (E)-1-(2-Naphthyl)-3-[2-(8-phenyloctyl)phenyl]-2-propen-1-one | C33H34O | 详情 | 详情 | |
| (IV) | 11415 | 2-Naphthyl[(2R,3S)-3-[2-(8-phenyloctyl)phenyl]oxiranyl]methanone | C33H34O2 | 详情 | 详情 | |
| (V) | 11416 | 2-naphthyl (2R,3S)-3-[2-(8-phenyloctyl)phenyl]-2-oxiranecarboxylate | C33H34O3 | 详情 | 详情 | |
| (VI) | 11417 | lithium (2R,3S)-3-[2-(8-phenyloctyl)phenyl]-2-oxiranecarboxylate | C23H27LiO3 | 详情 | 详情 | |
| (VII) | 11418 | methyl 3-sulfanylpropanoate; Methyl 3-mercaptopropionate | 2935-90-2 | C4H8O2S | 详情 | 详情 |
| (VIII) | 11419 | (2R,3S)-3-[2-(8-Phenyloctyl)phenyl]-2-oxiranecarboxamide | C23H29NO2 | 详情 | 详情 | |
| (IX) | 11420 | Methyl 3-sulfanylpropionate sodium salt | C4H7NaO2S | 详情 | 详情 | |
| (X) | 11421 | methyl 3-([(1R,2S)-3-amino-2-hydroxy-3-oxo-1-[2-(8-phenyloctyl)phenyl]propyl]sulfanyl)propanoate | C27H37NO4S | 详情 | 详情 | |
| (XI) | 11422 | 3-([(1R,2S)-3-Amino-2-hydroxy-3-oxo-1-[2-(8-phenyloctyl)phenyl]propyl]sulfanyl)propionic acid | C26H35NO4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The compound was prepared by Mannich reaction of 2-acetyl-naphthalene (I) with N-benzyl-N-isopropylamine hydrochloride (II) and formaldehyde.
| 【1】 Rankine, N.; Brown, G.R.; Bamford, A.M.; Culbert, E.J.; Bowyer, J.; James, D.S.; Tang, E.; Torr, V.; Naphthyl ketones: A new class of Janus kinase 3 inhibitors. Bioorg Med Chem Lett 2000, 10, 6, 575. |
合成路线3
该中间体在本合成路线中的序号：（V）
| 【1】 Van Wagenen BC,Moe ST,et al.2001.Prepantion of l-arylethylamines as calcium receptor ligands US 6211244 |
| 【2】 Wang X,ChenY,et aL 2004.Synthesis of cirutcalcet congeners Tetrahedron Lett, 45: 8355-8358 |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| （V） | 11413 | 1-(2-Naphthyl)-1-ethanone; Methyl 2-naphthyl ketone | 93-08-3 | C12H10O | 详情 | 详情 |
| (I) | 66196 | 2-Propenoyl chloride,3-[3-(trifluoromethyl)phenyl]-, (2E)-;2-Propenoylchloride, 3-[3-(trifluoromethyl)phenyl]-, (E)-;(E)-3-Trifluoromethylcinnamoylchloride;trans-3-(Trifluoromethyl)cinnamic acid chloride;trans-3-(Trifluoromethyl)cinnamoyl chloride;trans-3-[3-(Trifluoromethyl)phenyl]-2-propenoyl chloride | 64379-91-5 | C10H6ClF3O | 详情 | 详情 |
| (II) | 66197 | 2-Propenamide,3-[3-(trifluoromethyl)phenyl]-, (2E)-;2-Propenamide,3-[3-(trifluoromethyl)phenyl]-, (E)- | 64380-24-1 | C10H8F3NO | 详情 | 详情 |
| (III) | 66198 | 3-(3-(trifluoromethyl)phenyl)propanamide | C10H10F3NO | 详情 | 详情 | |
| (IV) | 66199 | 3-(3-(trifluoromethyl)phenyl)propan-1-amine | C10H12F3N | 详情 | 详情 | |
| (VI) | 66200 | (E)-N-(1-(naphthalen-1-yl)ethylidene)-3-(3-(trifluoromethyl)phenyl)propan-1-amine | C22H20F3N | 详情 | 详情 | |
| (VII) | 66201 | (R)-N-(1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine | C22H22F3N | 详情 | 详情 |