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【结 构 式】 
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【分子编号】13213 【品名】ethyl iminoformate 【CA登记号】 |
【 分 子 式 】C3H7NO 【 分 子 量 】73.09472 【元素组成】C 49.3% H 9.65% N 19.16% O 21.89% |
合成路线1
该中间体在本合成路线中的序号：(III)This compound can be obtained by two related ways: 1) By cyclization of aminomalonamide (I) with ethyl orthoformate (II) at 150 C catalyzed with acetic acid. 2) By cyclization of (I) with ethyl formimidate (III) at 150 C catalyzed with acetic acid.
| 【1】 Atsumi, T.; et al.; JP 7688965 . |
| 【2】 Atami, T.; et al.; JP 77118468 . |
| 【3】 Serradell, M.N.; Hopkins, S.J.; Castaner, J.; SM-108. Drugs Fut 1984, 9, 7, 525. |
合成路线2
该中间体在本合成路线中的序号：(II)The reaction of 14C-labeled cyanhydric acid (I) with HCl and ethanol gives the iminoester (II), which by reaction with more ethanol in chloroform yields the labeled orthoester (III). The cyclization of the triaminopyrimidinone (IV) with orthoester (III) by means of Ms-OH in chloroform affords the chloropurine derivative (V), which is finally hydrolyzed with NaOH to afford the target compound, the 14C-labeled carbovir.
| 【1】 Gopinathan, M.B.; Kepler, J.A.; Synthesis of carbon-14 labelled cis-2-amino-1,9-dihydro-9-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-H6-purine-6-one; [8-14C]carbovir: A promising anti-AIDS drug. J Label Compd Radiopharm 1991, 29, 6, 645. |
| 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) | 55517 | nitrilomethane | CHN | 详情 | 详情 | |
| (I) | 55518 | nitrilomethane | CHN | 详情 | 详情 | |
| (II) | 13213 | ethyl iminoformate | C3H7NO | 详情 | 详情 | |
| (II) | 55519 | ethyl iminoformate | C3H7NO | 详情 | 详情 | |
| (III) | 27311 | trimethoxymethane;Trimethyl orthoformate;Methyl orthoformate | 149-73-5 | C4H10O3 | 详情 | 详情 |
| (III) | 55520 | trimethoxymethane; dimethoxymethyl methyl ether | C4H10O3 | 详情 | 详情 | |
| (IV) | 17660 | [(1S,4R)-4-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]-2-cyclopenten-1-yl]methanol | C10H14ClN5O | 详情 | 详情 | |
| (V) | 17650 | [(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol | C11H12ClN5O | 详情 | 详情 | |
| (V) | 55521 | [(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol | C11H12ClN5O | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XXV)Compound (XIX) reacts with 4-mercapto-N,N-bis(p-nitrobenzyloxycarbonyl)pyrazolidine (XX) in the presence of diisopropylethylamine to give p-nitrobenzyl (1R,5R,6S)-2-[[N,N-bis(p-nitrobenzyloxycarbonyl)pyrazolidin-4-yl]thio]-6-[1(R)-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (XXIII). Compound (XXIII) is reduced with H2 over Pd/C to give (1R,5R,6S)-2-[[N,N-bis(p-nitrobenzyloxycarbonyl)pyrazolidin-4-yl]thio]-6-[1(R)-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylate (XXIV), which is finally reacted with ethylformimidate hydrochloride (XXV). Compound (XX) is obtained from epichlorohydrin (XXI) by treatment with hydrazine monohydrate followed by reaction with p-nitrobenzyloxycarbonyl chloride to give 4-hydroxy-N,N-bis(p-nitrobenzyloxycarbonyl)pyrazolidine (XXII), which is subsequently treated with methanesulfonyl chloride and triethylamine in dichloromethane, potassium acetate in acetone and sodium methoxide in methanol-THF. Compound (XX) can also be obtained from hydrazine hydrate using a longer alternative procedure.
| 【1】 Kumagai, T.; Matsunaga, H.; Machida, Y.; Nagase, Y.; Hikida, M.; Nagao, Y. (Lederle (Japan), Ltd.); (1R,5S,6S)-2-(Substd. thio)-6-[(R)-1-hydroxy-ethyl]-1-methyl-carbapenem-3-carboxylic-acid derivatives. AU 8814428; EP 0289801; JP 1989025779; US 4925836 . |
| 【2】 Abe, T.; Matsunaga, H.; Kumagai, T.; Nagase, Y. (Lederle (Japan), Ltd.); Method of preparation of carbapenem cpds. JP 1990088578 . |
| 【3】 Hayashi, T.; Shimada, O.; Inoue, Y.; Nagao, Y.; Matsunaga, H.; Nagase, Y.; Kumagai, T.; Abe, T.; beta-Lactams. 3. Asymmetric total synthesis of new non-natural 1beta-methylcarbapenems exhibiting strong antimicrobial activities and stability against human renal dehydropeptidase-. J Org Chem 1992, 57, 15, 4243-9. |
| 【4】 Rabasseda, X.; Prous, J.; Castaner, J.; Biapenem. Drugs Fut 1994, 19, 7, 631. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIX) | 13224 | 4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | 90776-59-3 | C29H27N2O10P | 详情 | 详情 |
| (XX) | 13208 | bis(4-nitrobenzyl) 4-sulfanyl-1,2-pyrazolidinedicarboxylate | C19H18N4O8S | 详情 | 详情 | |
| (XXI) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (XXII) | 13210 | bis(4-nitrobenzyl) 4-hydroxy-1,2-pyrazolidinedicarboxylate | C19H18N4O9 | 详情 | 详情 | |
| (XXIII) | 13211 | bis(4-nitrobenzyl) 4-([(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-2-[2-(4-nitrophenyl)acetyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]sulfanyl)-1,2-pyrazolidinedicarboxylate | C36H34N6O13S | 详情 | 详情 | |
| (XXIV) | 13212 | (4R,5S,6S)-3-[(1,2-bis[[(4-Nitrobenzyl)oxy]carbonyl]-4-pyrazolidinyl)sulfanyl]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid | C29H29N5O12S | 详情 | 详情 | |
| (XXV) | 13213 | ethyl iminoformate | C3H7NO | 详情 | 详情 |