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【结 构 式】 
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【分子编号】27196 【品名】3-(2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl)-2-[(phenylimino)methyl]propanenitrile 【CA登记号】 |
【 分 子 式 】C24H24N2O3 【 分 子 量 】388.46624 【元素组成】C 74.21% H 6.23% N 7.21% O 12.36% |
合成路线1
该中间体在本合成路线中的序号：(IX)The reaction of cyclopropanecarbonyl chloride (I) with bis(trimethylsilyl)acetylene (II) gives 1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-one (III), which is reduced with NaBH4 and CeCl3 in methanol to the corresponding propynol (IV). The condensation of (IV) with 3-hydroxy-4,5-dimethoxybenzaldehyde (V) by means of triphenylphosphine and dimethyl azodicarboxylate in toluene yields the expected propynyl ether (VI), which is cyclized in N,N-diethylaniline at 200 C affording 2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-carbaldehyde (VII). The condensation of (VII) with 3-anilinopropionitrile (VIII) by means of potassium tert-butoxide in DMSO gives the acrylonitrile (IX), which is finally cyclized with guanidine (X) by means of potassium tert-butoxide in ethanol. (1)
| 【1】 Sorbera, L.A.; Castañer, J.; Rabasseda, X.; Iclaprim. Drugs Fut 2004, 29, 3, 220. |
| 【2】 Masciadri, R. (F. Hoffmann-La Roche AG); Diaminopyrimidines, pharmaceutical compsns. containing them and their use as antibacterial. EP 0866791; JP 2000501399; US 5773446; WO 9720839 . |
| 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) | 14061 | Cyclopropanecarbonyl chloride; Cyclopropanecarboxylic acid chloride | 4023-34-1 | C4H5ClO | 详情 | 详情 |
| (II) | 27189 | trimethyl[2-(trimethylsilyl)ethynyl]silane | 14630-40-1 | C8H18Si2 | 详情 | 详情 |
| (III) | 27190 | 1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-one | C9H14OSi | 详情 | 详情 | |
| (IV) | 27191 | 1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-ol | C9H16OSi | 详情 | 详情 | |
| (V) | 27192 | 3-hydroxy-4,5-dimethoxybenzaldehyde | C9H10O4 | 详情 | 详情 | |
| (VI) | 27193 | 3-[[1-cyclopropyl-3-(trimethylsilyl)-2-propynyl]oxy]-4,5-dimethoxybenzaldehyde | C18H24O4Si | 详情 | 详情 | |
| (VII) | 27194 | 2-cyclopropyl-7,8-dimethoxy-2H-chromene-5-carbaldehyde | C15H16O4 | 详情 | 详情 | |
| (VIII) | 27195 | 3-anilinopropanenitrile | 1075-76-9 | C9H10N2 | 详情 | 详情 |
| (IX) | 27196 | 3-(2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl)-2-[(phenylimino)methyl]propanenitrile | C24H24N2O3 | 详情 | 详情 | |
| (X) | 14790 | Guanidine | 113-00-8 | CH5N3 | 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 reaction of cyclopropanecarbonyl chloride (I) with bis(trimethylsilyl)acetylene (II) gives 1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-one (III), which is reduced with NaBH4 and CeCl3 in methanol to the corresponding propynol (IV). The condensation of propynol (IV) with 3-hydroxy-4,5-dimethoxybenzoic acid methyl ester (XI) by means of triphenylphosphine and dimethyl azodicarboxylate in toluene yields the expected propynyl ether (XII), which is cyclized in N,N-diethylaniline at 200 C affording 2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-carboxylic acid methyl ester (XIII). Finally, this compound is reduced with NaAlH2(OCH2CH2)2 and morpholine in toluene to give the previously described 2-cyclopropyl-7,8-dimethoxy-2H-1-benzopyran-5-carbaldehyde (VII). The condensation of (VII) with 3-anilinopropionitrile (VIII) by means of potassium tert-butoxide in DMSO gives the acrylonitrile (IX), which is finally cyclized with guanidine (X) by means of potassium tert-butoxide in ethanol.
| 【1】 Masciadri, R. (F. Hoffmann-La Roche AG); Diaminopyrimidines, pharmaceutical compsns. containing them and their use as antibacterial. EP 0866791; JP 2000501399; US 5773446; WO 9720839 . |
| 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) | 14061 | Cyclopropanecarbonyl chloride; Cyclopropanecarboxylic acid chloride | 4023-34-1 | C4H5ClO | 详情 | 详情 |
| (II) | 27189 | trimethyl[2-(trimethylsilyl)ethynyl]silane | 14630-40-1 | C8H18Si2 | 详情 | 详情 |
| (III) | 27190 | 1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-one | C9H14OSi | 详情 | 详情 | |
| (IV) | 27191 | 1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-ol | C9H16OSi | 详情 | 详情 | |
| (VII) | 27194 | 2-cyclopropyl-7,8-dimethoxy-2H-chromene-5-carbaldehyde | C15H16O4 | 详情 | 详情 | |
| (VIII) | 27195 | 3-anilinopropanenitrile | 1075-76-9 | C9H10N2 | 详情 | 详情 |
| (IX) | 27196 | 3-(2-cyclopropyl-7,8-dimethoxy-2H-chromen-5-yl)-2-[(phenylimino)methyl]propanenitrile | C24H24N2O3 | 详情 | 详情 | |
| (X) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
| (XI) | 27197 | methyl 3-hydroxy-4,5-dimethoxybenzoate | C10H12O5 | 详情 | 详情 | |
| (XII) | 27198 | methyl 3-[[1-cyclopropyl-3-(trimethylsilyl)-2-propynyl]oxy]-4,5-dimethoxybenzoate | C19H26O5Si | 详情 | 详情 | |
| (XIII) | 27199 | methyl 2-cyclopropyl-7,8-dimethoxy-2H-chromene-5-carboxylate | C16H18O5 | 详情 | 详情 |