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【结 构 式】 
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【分子编号】11285 【品名】1-Methyl-1H-pyrrole; Methylpyrrole 【CA登记号】96-54-8 |
【 分 子 式 】C5H7N 【 分 子 量 】81.11732 【元素组成】C 74.03% H 8.7% N 17.27% |
合成路线1
该中间体在本合成路线中的序号：(I)The synthesis of [14C]-labeled prinomide has been described: The carboxylation of 1-methylpyrrole (I) with 14CO2 and butyllithium in THF gives labeled 1-methylpyrrole-2-carboxylic acid (II), which is esterified with diazomethane to the methyl ester (III). The reaction of (III) with acetonitrile by means of NaH in DMF affords 3-(1-methylpyrrol-2-yl)-3-oxopropanenitrile (IV) labeled in the carbonyl group. Finally, this compound is condensed with phenylisocyanate (V) by means of triethylamine in toluene, affording the prinomide labeled in the carbonyl group. The condensation of unlabeled (IV) with (V) labeled in the phenyl ring yields the corresponding prinomide labeled in the aromatic ring.
| 【1】 Chaudhuri, N.K.; Markus, B.; Synthesis of two 14C-labeled forms of prinomide, a potential anti-inflammatory compound and its hydroxy metabolite, labeled with 14C. J Label Compd Radiopharm 1990, 28, 3, 321. |
| 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) | 11286 | 1-Methyl-1H-pyrrole-2-carboxylic acid; 1-Methyl-2-pyrrolecarboxylic acid | 6973-60-0 | C6H7NO2 | 详情 | 详情 |
| (II) | 45058 | 1-methyl-1H-pyrrole-2-carboxylic acid | C6H7NO2 | 详情 | 详情 | |
| (III) | 11287 | methyl 1-methyl-1H-pyrrole-2-carboxylate | 37619-24-2 | C7H9NO2 | 详情 | 详情 |
| (III) | 45059 | methyl 1-methyl-1H-pyrrole-2-carboxylate | C7H9NO2 | 详情 | 详情 | |
| (IV) | 11288 | 3-(1-Methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile | C8H8N2O | 详情 | 详情 | |
| (IV) | 45060 | 3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile | C8H8N2O | 详情 | 详情 | |
| (V) | 11289 | 1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate | 103-71-9 | C7H5NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Alkylation of imidazole (I) with 1,7-dibromoheptane (II) by means of potassium (metal) in refluxing THF furnishes N,N'-bis-(1-imidazolyl)heptane (III), which is treated with trichloroacetyl chloride (IV) in CH2Cl2 to provide derivative (V). Nitration of (V) by means of nitric acid/sulfuric acid in Ac2O/CH2Cl2 yields compound (VI), which is then converted into intermediate (VIII) by coupling in DMF/THF with substituted pyrrole (VII). In turn, (VII) can be obtained as follows: Treatment of N-methylpyrrole (IX) with trichloroacetyl chloride (IV) in CH2Cl2 affords derivative (X), which is nitrated to yield compound (XI) in the same conditions as for nitration of (V). The last step involves coupling of (XI) with 3-(dimethylamino)propylamine (XII), followed by reduction of the nitro moiety by hydrogenation over Pd/C in DMF/MeOH. Finally, the target product can be obtained by first hydrogenation of intermediate (VIII) over Pd/C in DMF/MeOH, followed by reaction with DCC and HOBt in DMF to allow coupling with carboxylic acid (XIV), which can be obtained by saponification of ethyl ester (XIII) in EtOH.
| 【1】 Sharma, S.K.; et al.; Design and synthesis of novel thiazole-containing cross-linked polyamides related to tha antiviral antibiotic distamycin. J Org Chem 2000, 65, 4, 1102. |
| 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) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
| (II) | 47013 | 1,7-dibromoheptane | 4549-31-9 | C7H14Br2 | 详情 | 详情 |
| (III) | 47014 | 1-[7-(1H-imidazol-1-yl)heptyl]-1H-imidazole | C13H20N4 | 详情 | 详情 | |
| (IV) | 47015 | 2,2,2-trichloroacetyl chloride | 76-02-8 | C2Cl4O | 详情 | 详情 |
| (V) | 47016 | 2,2,2-trichloro-1-(1-[7-[2-(2,2,2-trichloroacetyl)-1H-imidazol-1-yl]heptyl]-1H-imidazol-2-yl)-1-ethanone | C17H18Cl6N4O2 | 详情 | 详情 | |
| (VI) | 47017 | 2,2,2-trichloro-1-(4-nitro-1-[7-[4-nitro-2-(2,2,2-trichloroacetyl)-1H-imidazol-1-yl]heptyl]-1H-imidazol-2-yl)-1-ethanone | C17H16Cl6N6O6 | 详情 | 详情 | |
| (VII) | 47018 | 4-amino-N-[3-(dimethylamino)propyl]-1-methyl-1H-pyrrole-2-carboxamide | C11H20N4O | 详情 | 详情 | |
| (VIII) | 47019 | N-[5-([[3-(dimethylamino)propyl]amino]carbonyl)-1-methyl-1H-pyrrol-3-yl]-1-[7-[2-([[5-([[3-(dimethylamino)propyl]amino]carbonyl)-1-methyl-1H-pyrrol-3-yl]amino]carbonyl)-4-nitro-1H-imidazol-1-yl]heptyl]-4-nitro-1H-imidazole-2-carboxamide | C37H54N14O8 | 详情 | 详情 | |
| (IX) | 11285 | 1-Methyl-1H-pyrrole; Methylpyrrole | 96-54-8 | C5H7N | 详情 | 详情 |
| (X) | 47020 | 2,2,2-trichloro-1-(1-methyl-1H-pyrrol-2-yl)-1-ethanone | C7H6Cl3NO | 详情 | 详情 | |
| (XI) | 47021 | 2,2,2-trichloro-1-(1-methyl-4-nitro-1H-pyrrol-2-yl)-1-ethanone | C7H5Cl3N2O3 | 详情 | 详情 | |
| (XII) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (XIII) | 47022 | ethyl 2-amino-4-methylthiazole-5-carboxylate; ethyl 2-amino-4-methyl-1,3-thiazole-5-carboxylate | 7210-76-6 | C7H10N2O2S | 详情 | 详情 |
| (XIV) | 47023 | 2-amino-4-methyl-1,3-thiazole-5-carboxylic acid | C5H6N2O2S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)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 |