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【结 构 式】 
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【分子编号】27195 【品名】3-anilinopropanenitrile 【CA登记号】1075-76-9 |
【 分 子 式 】C9H10N2 【 分 子 量 】146.19188 【元素组成】C 73.94% H 6.89% N 19.16% |
合成路线1
该中间体在本合成路线中的序号：(VIII)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：(VIII)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 |
合成路线3
该中间体在本合成路线中的序号：(III)Methylation of 5-iodovanillin (I) with dimethyl sulfate and K2CO3 afforded dimethoxy derivative (II). This was condensed with 3-anilinopropionitrile (III) in the presence of potassium tert-butoxide yielding the enamino nitrile (IV). Subsequent cyclization of (IV) with guanidine hydrochloride (V) produced diaminopyrimidine (VI).
| 【1】 Guerry, P.; Locher, H.H.; Hubschwerlen, C.; Wyss, P.C.; Jolidon, S.; Hartman, P.G.; Stalder, H.; Specklin, J.L.; Anti-MRSA dihydrofolate reductase inhibitors: Synthesis and SAR. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F1800. |
| 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) | 12758 | 4-Hydroxy-3-iodo-5-methoxybenzaldehyde; 5-Iodovanillin | 5438-36-8 | C8H7IO3 | 详情 | 详情 |
| (II) | 40641 | 3-iodo-4,5-dimethoxybenzaldehyde | 32024-15-0 | C9H9IO3 | 详情 | 详情 |
| (III) | 27195 | 3-anilinopropanenitrile | 1075-76-9 | C9H10N2 | 详情 | 详情 |
| (IV) | 40642 | (Z)-3-anilino-2-(3-iodo-4,5-dimethoxybenzyl)-2-propenenitrile | C18H17IN2O2 | 详情 | 详情 | |
| (V) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
| (VI) | 40643 | 5-(3-iodo-4,5-dimethoxybenzyl)-2,4-pyrimidinediamine; 2-amino-5-(3-iodo-4,5-dimethoxybenzyl)-4-pyrimidinylamine | C13H15IN4O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(III)Methylation of 5-iodovanillin (I) with dimethyl sulfate and K2CO3 afforded dimethoxy derivative (II). This was condensed with 3-anilinopropionitrile (III) in the presence of potassium tert-butoxide yielding the enamino nitrile (IV). Subsequent cyclization of (IV) with guanidine hydrochloride (V) produced diaminopyrimidine (VI). Cinnamate derivative (VIII) was then obtained by palladium-catalyzed coupling of (VI) with ethyl acrylate (VII).
| 【1】 Guerry, P.; Locher, H.H.; Hubschwerlen, C.; Wyss, P.C.; Jolidon, S.; Hartman, P.G.; Stalder, H.; Specklin, J.L.; Anti-MRSA dihydrofolate reductase inhibitors: Synthesis and SAR. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F1800. |
| 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) | 12758 | 4-Hydroxy-3-iodo-5-methoxybenzaldehyde; 5-Iodovanillin | 5438-36-8 | C8H7IO3 | 详情 | 详情 |
| (II) | 40641 | 3-iodo-4,5-dimethoxybenzaldehyde | 32024-15-0 | C9H9IO3 | 详情 | 详情 |
| (III) | 27195 | 3-anilinopropanenitrile | 1075-76-9 | C9H10N2 | 详情 | 详情 |
| (IV) | 40642 | (Z)-3-anilino-2-(3-iodo-4,5-dimethoxybenzyl)-2-propenenitrile | C18H17IN2O2 | 详情 | 详情 | |
| (V) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
| (VI) | 40643 | 5-(3-iodo-4,5-dimethoxybenzyl)-2,4-pyrimidinediamine; 2-amino-5-(3-iodo-4,5-dimethoxybenzyl)-4-pyrimidinylamine | C13H15IN4O2 | 详情 | 详情 | |
| (VII) | 10164 | ethyl acrylate | 140-88-5 | C5H8O2 | 详情 | 详情 |
| (VIII) | 40649 | ethyl (E)-3-[5-[(2,4-diamino-5-pyrimidinyl)methyl]-2,3-dimethoxyphenyl]-2-propenoate | C18H22N4O4 | 详情 | 详情 |