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【结 构 式】 
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【分子编号】53514 【品名】methyl 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate 【CA登记号】n/a |
【 分 子 式 】C24H30N6O6 【 分 子 量 】498.53904 【元素组成】C 57.82% H 6.07% N 16.86% O 19.26% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of 4-(tert-butoxycarbonylamino)-1-methyl-1H-pyrrole-2-carboxylic acid (I) with 4-amino-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester (II) by means of DCC, HOBT and TEA in hot DMF gives the dimeric amide (III), which is hydrolyzed with NaOH in hot methanol/water to yield the carboxylic acid (IV). The condensation of (IV) with methyl ester (II) by means of HBTU and TEA in hot DMF affords the trimeric diamide (V), which is hydrolyzed with NaOH in methanol/water to provide the carboxylic acid (VI). The deprotection of the carbamate group of (VI) with HCl in ethyl acetate gives the trimeric amino acid (VII), which is condensed with 4,5-dichloroisothiazole-3-carboxylic acid (VIII) by means of HBTU and DIEA in DMF to yield the tetrameric carboxylic acid (IX). The condensation of (IX) with 3-aminopropionitrile (X) by means of HBTU and TEA in DMF affords the corresponding tetrameric tetraamide (XI), which is treated with gaseous HCl in methanol to provide the iminoester (XII). Finally, this compound is treated with NH3 in methanol to furnish the target carboxamidine.
| 【1】 Burli, R.; et al.; HARP: A novel class of antibiotics. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-1685. |
| 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) | 53510 | 4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid | 77716-11-1 | C11H16N2O4 | 详情 | 详情 |
| (II) | 53511 | methyl 4-amino-1-methyl-1H-pyrrole-2-carboxylate | 180258-45-1 | C7H10N2O2 | 详情 | 详情 |
| (III) | 53512 | methyl 4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate | n/a | C18H24N4O5 | 详情 | 详情 |
| (IV) | 53513 | 4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid | n/a | C17H22N4O5 | 详情 | 详情 |
| (V) | 53514 | methyl 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate | n/a | C24H30N6O6 | 详情 | 详情 |
| (VI) | 53515 | 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid | n/a | C23H28N6O6 | 详情 | 详情 |
| (VII) | 53516 | 4-{[(4-{[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrole-2-carboxylic acid | n/a | C18H20N6O4 | 详情 | 详情 |
| (VIII) | 53517 | 4,5-Dichloroisothiazole-3-carboxylic acid | 131947-13-2 | C4HCl2NO2S | 详情 | 详情 |
| (IX) | 53518 | 4-{[(4-{[(4-{[(4,5-dichloro-3-isothiazolyl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrole-2-carboxylic acid | n/a | C22H19Cl2N7O5S | 详情 | 详情 |
| (X) | 38094 | 3-aminopropanenitrile | 151-18-8 | C3H6N2 | 详情 | 详情 |
| (XI) | 53519 | 4,5-dichloro-N-(5-{[(5-{[(5-{[(2-cyanoethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)-3-isothiazolecarboxamide | n/a | C25H23Cl2N9O4S | 详情 | 详情 |
| (XII) | 53520 | methyl 3-{[(4-{[(4-{[(4-{[(4,5-dichloro-3-isothiazolyl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}propanimidoate | n/a | C26H27Cl2N9O5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)Friedel-Crafts acylation of N-methylpyrrole (I) with trichloroacetyl chloride (II) affords the pyrrolyl ketone (III), which is subsequently subjected to electrophilic nitration with in situ generated acetyl nitrate, producing nitropyrrole (IV). Cleavage of the trichloroketone group of (IV) under alkaline conditions, followed by Fischer esterification leads to methyl ester (V). The nitro group of (V) is then reduced to amine (VI) by catalytic hydrogenation over Pd/C. After protection of amine (VI) as the corresponding N-Boc derivative (VII), saponification of the methyl ester group of (VII) yields acid (VIII). Coupling between the pyrrolecarboxylic acid (VIII) and amino ester (VI) provides the amide adduct (IX). After alkaline ester hydrolysis in (IX), the resultant carboxylic acid (X) is coupled with a further moiety of methyl 4-amino-1-methylpyrrole-2-carboxylate (VI) to furnish the tripyrrolyl compound (XI). Subsequent methyl ester saponification in (XI) provides acid (XII).
| 【1】 Ge, Y.; Taylor, M.J.; Baird, E.E.; Moser, H.E.; Burli, R.W. (GeneSoft, Inc.); Charged cpds. comprising a nucleic acid binding moiety and uses therefor. JP 2003529609; WO 0174898 . |
| 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) | 11285 | 1-Methyl-1H-pyrrole; Methylpyrrole | 96-54-8 | C5H7N | 详情 | 详情 |
| (II) | 47015 | 2,2,2-trichloroacetyl chloride | 76-02-8 | C2Cl4O | 详情 | 详情 |
| (III) | 47020 | 2,2,2-trichloro-1-(1-methyl-1H-pyrrol-2-yl)-1-ethanone | C7H6Cl3NO | 详情 | 详情 | |
| (IV) | 47021 | 2,2,2-trichloro-1-(1-methyl-4-nitro-1H-pyrrol-2-yl)-1-ethanone | C7H5Cl3N2O3 | 详情 | 详情 | |
| (V) | 58474 | methyl 1-methyl-4-nitro-1H-pyrrole-2-carboxylate | C7H8N2O4 | 详情 | 详情 | |
| (VI) | 53511 | methyl 4-amino-1-methyl-1H-pyrrole-2-carboxylate | 180258-45-1 | C7H10N2O2 | 详情 | 详情 |
| (VII) | 58475 | methyl 4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate | C12H18N2O4 | 详情 | 详情 | |
| (VIII) | 53510 | 4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid | 77716-11-1 | C11H16N2O4 | 详情 | 详情 |
| (IX) | 53512 | methyl 4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate | n/a | C18H24N4O5 | 详情 | 详情 |
| (X) | 53513 | 4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid | n/a | C17H22N4O5 | 详情 | 详情 |
| (XI) | 53514 | methyl 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylate | n/a | C24H30N6O6 | 详情 | 详情 |
| (XII) | 53515 | 4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid | n/a | C23H28N6O6 | 详情 | 详情 |