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【结 构 式】 
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【分子编号】41443 【品名】N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide 【CA登记号】 |
【 分 子 式 】C21H26N10O5 【 分 子 量 】498.50184 【元素组成】C 50.6% H 5.26% N 28.1% O 16.05% |
合成路线1
该中间体在本合成路线中的序号：(X)The known tripyrrole carboxylic acid derivative (IX) was coupled with aminoethylguanidine (IV) by means of DCC and HOBt to afford amide (X). The nitro group of (X) was reduced by catalytic hydrogenation over Pd/C, and the resulting amine (XI) was finally coupled with acid chloride (VIII) under Schotten-Baumann conditions yielding the title amide.
| 【1】 Cozzi, P.; Beria, I.; Biasoli, G.; Caldarelli, M.; Capolongo, L.; Franzetti, C. (Pharmacia & Upjohn AB); Acryloyl substd. distamycin derivs., process for preparing them, and their use as antitumor and antiviral agents. WO 9804524 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 41437 | N-(2-aminoethyl)guanidine | C3H10N4 | 详情 | 详情 | |
| (VIII) | 41441 | 4-[(2-bromoacryloyl)amino]-1-methyl-1H-pyrrole-2-carbonyl chloride | C9H8BrClN2O2 | 详情 | 详情 | |
| (IX) | 41442 | 1-methyl-4-[[(1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxylic acid | C18H18N6O6 | 详情 | 详情 | |
| (X) | 41443 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide | C21H26N10O5 | 详情 | 详情 | |
| (XI) | 41444 | N-(2-[[amino(imino)methyl]amino]ethyl)-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-carboxamide | C21H28N10O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)In a related procedure, aminoethylguanidine (IV) was treated with 1-methyl-4-nitropyrrole-2-carbonyl chloride (XII) producing amide (XIII). Catalytic hydrogenation of the nitro group of (XIII) gave amine (XIV), which was again coupled with acid chloride (XII). The resulting adduct (XV) was then subjected to a new hydrogenation-coupling cycle providing the tripyrrole derivative (X).
| 【1】 Cozzi, P.; et al.; Cytotoxic alpha-bromoacrylic derivatives of distamycin analogues modified at the amidino moiety. Bioorg Med Chem Lett 2000, 10, 11, 1273. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 41437 | N-(2-aminoethyl)guanidine | C3H10N4 | 详情 | 详情 | |
| (X) | 41443 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide | C21H26N10O5 | 详情 | 详情 | |
| (XII) | 27852 | 1-methyl-4-nitro-1H-pyrrole-2-carbonyl chloride | C6H5ClN2O3 | 详情 | 详情 | |
| (XIII) | 41445 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide | C9H14N6O3 | 详情 | 详情 | |
| (XIV) | 41446 | 4-amino-N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-1H-pyrrole-2-carboxamide | C9H16N6O | 详情 | 详情 | |
| (XV) | 41447 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide | C15H20N8O4 | 详情 | 详情 | |
| (XVI) | 41448 | N-(2-[[amino(imino)methyl]amino]ethyl)-4-[[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrole-2-carboxamide | C15H22N8O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XII)The reaction of ethylenediamine (I) with Boc2O in dioxane gives the monocarbamate (II), which is condensed with O-methylisourea (III) to yield the aminoguanidine carbamate (IV). The cleavage of the carbamate group of (IV) by means of HCl in methanol affords the aminoguanidine (V), which is condensed with 1-methyl-4-nitropyrrole-2-carbonyl chloride (VI) by means of NaHCO3 in dioxane/water to provide the amide (VII). The reduction of the nitro group of (VII) by means of H2 over Pd/C in 1N HCl affords the 4-aminopyrrole-2-carboxamide (VIII), which is condensed with the acid chloride (VI) as before to give the diamide (IX). Reduction of the nitro group of (IX) under the same conditions described above yields the amino diamide (X), which is condensed with the 14-labeled acid chloride (XI) as described above to afford the triamide (XII). Further reduction of the nitro group of (XII) gives the amino triamide (XIII), which is finally condensed with 4-(2-bromopropenamido)-1-methylpyrrole-2-carbonyl chloride (XIV) by means of NaHCO3 in dioxane/water to yield the target 14C labeled pentaamide compound.
| 【1】 Fontana, E.; Pignatti, A.; Synthesis of brostallicin (PNU-166196A) labelled with 2H and 14C. Label. Cop. & Radiopharm. 2002, 45, 11, 899. |
| 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) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (II) | 13241 | N-Boc-ethylenediamine;tert-butyl (2-aminoethyl)carbamate；tert-butyl 2-aminoethylcarbamate; tert-Butyl n-(2-aminoethyl)carbamate | 57260-73-8 | C7H16N2O2 | 详情 | 详情 |
| (III) | 26657 | O-methyl isourea; [Amino(imino)methoxy]methane | 52328-05-9 | C2H6N2O | 详情 | 详情 |
| (IV) | 41436 | tert-butyl 2-[[amino(imino)methyl]amino]ethylcarbamate | C8H18N4O2 | 详情 | 详情 | |
| (V) | 41437 | N-(2-aminoethyl)guanidine | C3H10N4 | 详情 | 详情 | |
| (VI) | 27852 | 1-methyl-4-nitro-1H-pyrrole-2-carbonyl chloride | C6H5ClN2O3 | 详情 | 详情 | |
| (VII) | 41445 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide | C9H14N6O3 | 详情 | 详情 | |
| (VIII) | 41446 | 4-amino-N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-1H-pyrrole-2-carboxamide | C9H16N6O | 详情 | 详情 | |
| (IX) | 41447 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide | C15H20N8O4 | 详情 | 详情 | |
| (X) | 41448 | N-(2-[[amino(imino)methyl]amino]ethyl)-4-[[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrole-2-carboxamide | C15H22N8O2 | 详情 | 详情 | |
| (XI) | 65171 | 1-methyl-4-nitro-1H-pyrrole-2-carbonyl chloride | 28494-51-1 | C6H5ClN2O3 | 详情 | 详情 |
| (XII) | 41443 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide | C21H26N10O5 | 详情 | 详情 | |
| (XIII) | 61732 | 4-amino-N-(5-{[(5-{[(2-{[amino(imino)methyl]amino}ethyl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)amino]carbonyl}-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide | C21H28N10O3 | 详情 | 详情 | |
| (XIV) | 41441 | 4-[(2-bromoacryloyl)amino]-1-methyl-1H-pyrrole-2-carbonyl chloride | C9H8BrClN2O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XI)The reaction of deuterium labeled ethylenediamine (I) with Boc2O in dioxane gives the monocarbamate (II), which is condensed with O-methylisourea (III) to yield the labeled aminoguanidine carbamate (IV). The cleavage of the carbamate group of (IV) by means of HCl in methanol affords the aminoguanidine (V), which is condensed with 1-methyl-4-nitropyrrole-2-carbonyl chloride (VI) by means of NaHCO3 in dioxane/water to provide the amide (VII). The reduction of the nitro group of (VII) by means of H2 over Pd/C in 1N HCl affords the 4-aminopyrrole-2-carboxamide (VIII), which is condensed with the acid chloride (VI) as before to give the diamide (IX). Reduction of the nitro group of (IX) under the same conditions described above yields the amino diamide (X), which is condensed with acid chloride (VI) as described above to afford the triamide (XI). Further reduction of the nitro group of (XI) gives the amino triamide (XII), which is finally condensed with 4-(2-bromopropenamido)-1-methylpyrrole-2-carbonyl chloride (XIII) by means of NaHCO3 in dioxane/water to yield the target deuterium labeled pentaamide compound.
| 【1】 Fontana, E.; Pignatti, A.; Synthesis of brostallicin (PNU-166196A) labelled with 2H and 14C. Label. Cop. & Radiopharm. 2002, 45, 11, 899. |
| 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) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (II) | 13241 | N-Boc-ethylenediamine;tert-butyl (2-aminoethyl)carbamate；tert-butyl 2-aminoethylcarbamate; tert-Butyl n-(2-aminoethyl)carbamate | 57260-73-8 | C7H16N2O2 | 详情 | 详情 |
| (III) | 26657 | O-methyl isourea; [Amino(imino)methoxy]methane | 52328-05-9 | C2H6N2O | 详情 | 详情 |
| (IV) | 41436 | tert-butyl 2-[[amino(imino)methyl]amino]ethylcarbamate | C8H18N4O2 | 详情 | 详情 | |
| (V) | 41437 | N-(2-aminoethyl)guanidine | C3H10N4 | 详情 | 详情 | |
| (VI) | 27852 | 1-methyl-4-nitro-1H-pyrrole-2-carbonyl chloride | C6H5ClN2O3 | 详情 | 详情 | |
| (VII) | 41445 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide | C9H14N6O3 | 详情 | 详情 | |
| (VIII) | 41446 | 4-amino-N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-1H-pyrrole-2-carboxamide | C9H16N6O | 详情 | 详情 | |
| (IX) | 41447 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide | C15H20N8O4 | 详情 | 详情 | |
| (X) | 41448 | N-(2-[[amino(imino)methyl]amino]ethyl)-4-[[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino]-1-methyl-1H-pyrrole-2-carboxamide | C15H22N8O2 | 详情 | 详情 | |
| (XI) | 41443 | N-(2-[[amino(imino)methyl]amino]ethyl)-1-methyl-4-[[(1-methyl-4-[[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrol-2-yl)carbonyl]amino]-1H-pyrrole-2-carboxamide | C21H26N10O5 | 详情 | 详情 | |
| (XII) | 41444 | N-(2-[[amino(imino)methyl]amino]ethyl)-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-carboxamide | C21H28N10O3 | 详情 | 详情 | |
| (XIII) | 41441 | 4-[(2-bromoacryloyl)amino]-1-methyl-1H-pyrrole-2-carbonyl chloride | C9H8BrClN2O2 | 详情 | 详情 |