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【结 构 式】 
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【分子编号】21674 【品名】1H-pyrrole 【CA登记号】109-97-7 |
【 分 子 式 】C4H5N 【 分 子 量 】67.09044 【元素组成】C 71.61% H 7.51% N 20.88% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction between pyrrole (I) and 3,4-difluoronitrobenzene (II) afforded the N-aryl pyrrole (III). Selective reduction of the nitro group of (III) by hydrogenation over sulfided platinum on carbon gave aniline (IV), which was converted to carbamate (V) upon treatment with benzyl chloroformate. Subsequent condensation of (V) with (R)-(-)-glycidyl butyrate (VI) in the presence of lithium bis(trimethylsilyl)amide produced the chiral oxazolidinone (VII). Mesylation of the alcohol group of (VII), followed by displacement with NaN3 yielded azide (VIII). This was reduced by hydrogenation over Pt/C/S to give amine (IX), which was finally acetylated using Ac2O and pyridine.
| 【1】 Emmert, D.E.; Reischer, R.J.; Ford, C.W.; Garmon, S.A.; Zurenko, G.E.; Barbachyn, M.R.; Hutchinson, D.K.; Stelzer, L.S.; Hester, J.B.; Synthesis and antibacterial activity of azolylphenyloxazolidinones having nitrogen-bound five-membered heterocyclic rings. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-137. |
| 【2】 Hutchinson, D.K. (Pharmacia & Upjohn AB); Hetero-aromatic ring substd. phenyloxazolidinone antimicrobials. EP 0807112; JP 1998513446; US 5910504; WO 9623788 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 | |
| (I) | 21674 | 1H-pyrrole | 109-97-7 | C4H5N | 详情 | 详情 |
| (II) | 17013 | 1,2-difluoro-4-nitrobenzene; 3,4-Difluoronitrobenzene | 369-34-6 | C6H3F2NO2 | 详情 | 详情 |
| (III) | 29412 | 1-(2-fluoro-4-nitrophenyl)-1H-pyrrole | C10H7FN2O2 | 详情 | 详情 | |
| (IV) | 29413 | 3-fluoro-4-(1H-pyrrol-1-yl)phenylamine3-fluoro-4-(1H-pyrrol-1-yl)aniline | C10H9FN2 | 详情 | 详情 | |
| (V) | 29414 | benzyl 3-fluoro-4-(1H-pyrrol-1-yl)phenylcarbamate | C18H15FN2O2 | 详情 | 详情 | |
| (VI) | 18385 | (2R)oxiranylmethyl butyrate;(R)-glycidyl butyrate | 60456-26-0 | C7H12O3 | 详情 | 详情 |
| (VII) | 29415 | (5R)-3-[3-fluoro-4-(1H-pyrrol-1-yl)phenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one | C14H13FN2O3 | 详情 | 详情 | |
| (VIII) | 29416 | (5R)-5-(azidomethyl)-3-[3-fluoro-4-(1H-pyrrol-1-yl)phenyl]-1,3-oxazolidin-2-one | C14H12FN5O2 | 详情 | 详情 | |
| (IX) | 29417 | (5S)-5-(aminomethyl)-3-[3-fluoro-4-(1H-pyrrol-1-yl)phenyl]-1,3-oxazolidin-2-one | C14H14FN3O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Condensation of N-(tert-butoxycarbonyl)phenylalanine methyl ester (I) with pyrrolyl magnesium bromide (generated from pyrrole (II) and MeMgBr) furnished ketone (III). The N-Boc group of (III) was deprotected with HCl in dioxan to yield aminoketone (IV), which was then condensed with the succinate building block (V) in DMF to afford succinamide (VI). Further deprotection of the tert-butyl ester of (VI) by treatment with trifluoroacetic acid provided carboxylic acid (VII), which was coupled with O-tert-butyldimethylsilyl hydroxylamine (VIII) in the presence of EDC and HOBt to yield, after desilylation, the target hydroxamic acid.
| 【1】 Sheppard, G.S.; Florjancic, A.S.; Giesler, J.R.; Xu, L.; Guo, Y.; Davidsen, S.K.; Marcotte, P.A.; Elmore, I.; Albert, D.H.; Terrance, J.M.; Bouska, J.J.; Goodfellow, C.L.; Morgan, D.W.; Summers, J.B.; Aryl ketones as novel replacements for the C-terminal amide bond of succinyl hydroxamate MMP inhibitors. Bioorg Med Chem Lett 1998, 8, 22, 3251. |
| 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) | 21673 | methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate | C15H21NO4 | 详情 | 详情 | |
| (II) | 21674 | 1H-pyrrole | 109-97-7 | C4H5N | 详情 | 详情 |
| (III) | 21675 | tert-butyl (1S)-1-benzyl-2-oxo-2-(1H-pyrrol-2-yl)ethylcarbamate | C18H22N2O3 | 详情 | 详情 | |
| (IV) | 21676 | (2S)-2-amino-3-phenyl-1-(1H-pyrrol-2-yl)-1-propanone hydrochloride | C13H15ClN2O | 详情 | 详情 | |
| (V) | 21641 | 1-(tert-butyl) 4-(2,3,4,5,6-pentafluorophenyl) (2S,3R)-2-allyl-3-isobutylbutanedioate | C21H25F5O4 | 详情 | 详情 | |
| (VI) | 21678 | tert-butyl (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoate | C28H38N2O4 | 详情 | 详情 | |
| (VII) | 21679 | (2S)-2-[(1R)-1-([[(1S)-1-benzyl-2-oxo-2-(1H-pyrrol-2-yl)ethyl]amino]carbonyl)-3-methylbutyl]-4-pentenoic acid | C24H30N2O4 | 详情 | 详情 | |
| (VIII) | 21644 | (Aminooxy)(tert-butyl)dimethylsilane; O-[tert-Butyl(dimethyl)silyl]hydroxylamine | 41879-39-4 | C6H17NOSi | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)Lithiation of 3-fluoropyridine (I) followed by formylation with methyl formate afforded aldehyde (II). Porphyrin (IV) was then prepared by condensation of aldehyde (II) with pyrrole (III) in refluxing propionic acid. Methylation of (IV) using methyl p-toluenesulfonate then gave the title pyridinium tosylate salt.
| 【1】 Shin, J.-H.; Namgoong, S.K.; Kim, H.-S.; Moon, S.C.; Jeong, B.H.; Lee, B.S.; Yu, B.S.; Lee, J.-S.; Synthesis of tetrakis(multifluoro-4-pyridyl)porphin derivatives as acetylcholinesterase inhibitors. Bioorg Med Chem Lett 2000, 10, 13, 1435. |
| 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) | 46855 | 3-fluoropyridine | 372-47-4 | C5H4FN | 详情 | 详情 |
| (II) | 46856 | 3-fluoroisonicotinaldehyde | C6H4FNO | 详情 | 详情 | |
| (III) | 21674 | 1H-pyrrole | 109-97-7 | C4H5N | 详情 | 详情 |
| (IV) | 46857 | 2,7,12,17-tetrakis(3-fluoro-4-pyridinyl)-21,22,23,24-tetraazapentacyclo[16.2.1.1(3,6).1(8,11).1(13,16)]tetracosa-1,3,5,7,9,11(23),12,14,16,18(21),19-undecaene | C40H22F4N8 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)Tetrakis-(2-pyridyl)porphyrin (III) was prepared by condensation between pyridine-2-carboxaldehyde (I) and pyrrole (II) in refluxing propionic acid. Metallation of porphyrin (III) was performed with MnCl2, which spontaneously underwent oxidation, yielding the Mn3+ complex (IV). Subsequent N-alkylation of the pyridine rings with ethyl iodide produced the corresponding pyridinium iodide salt, which was transformed to the analogous chloride by treatment with tetrabutylammonium chloride (1). In an alternative procedure, initial quaternization of the pyridine rings of porphyrin (III) with ethyl p-toluenesulfonate afforded (V), which was further metallated with MnCl2 to give the title compound.
| 【2】 Kachadourian, R.; et al.; Synthesis and superoxide dismuting activities of partially (1-4) beta-chlorinated derivatives of manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl)porphyrin. Inorg Chem 1999, 38, 2, 391. |
| 【3】 Bloodsworth, A.; et al.; Manganese-porphyrin reactions with lipid and lipoproteins. Free Radical Biol Med 2000, 28, 7, 1017. |
| 【4】 Batinic-Haberle, I.; Fridovich, I. (Duke University); Substd. porphyrins. EP 1045851; JP 2001521939; WO 9923097 . |
| 【1】 Batinié-Haberle, I.; et al.; Relationships among redox potentials, proton dissociation constants of pyrrolic nitrogens, and in vivo and in vitro superoxide dismutating activities of magnase(III) and iron(III) water-soluble porphyrins. Inorg Chem 1999, 38, 18, 4011. |
| 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) | 25173 | 2-pyridinecarbaldehyde | 1121-60-4 | C6H5NO | 详情 | 详情 |
| (II) | 21674 | 1H-pyrrole | 109-97-7 | C4H5N | 详情 | 详情 |
| (III) | 51699 | 2,7,12,17-tetra(2-pyridinyl)-21,22,23,24-tetraazapentacyclo[16.2.1.1(3,6).1(8,11).1(13,16)]tetracosa-1,3,5,7,9,11(23),12,14,16,18(21),19-undecaene | C40H26N8 | 详情 | 详情 | |
| (IV) | 51700 | C40H24MnN8 | 详情 | 详情 | ||
| (V) | 51701 | 1-ethyl-2-[7,12,17-tris(1-ethyl-2-pyridiniumyl)-21,22,23,24-tetraazapentacyclo[16.2.1.1(3,6).1(8,11).1(13,16)]tetracosa-1,3,5,7,9,11(23),12,14,16,18(21),19-undecaen-2-yl]pyridinium | C48H46N8 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)The tetraimidazolyl porphyrin (III) was prepared by reaction between 1-ethylimidazole-2-carboxaldehyde (I) and pyrrole (II) in refluxing propionic acid. Quaternization of the imidazole groups of (III) with iodoethane furnished the tetrakis-imidazolium iodide salt (IV). After complexation of porphyrin (IV) with manganese(III) acetate, its precipitation as the hexafluorophosphate salt followed by anion exchange with tetrabutylammonium chloride, furnished the title chelate pentachloride salt.
| 【1】 Trova, M.P.; Kitchen, D.B.; Crapo, J.D.; Gauuan, P.J.F.; Day, B.J. (National Jewish Medical and Research Center); Substd. porphyrins. EP 1155019; JP 2002535332; WO 0043395 . |
| 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) | 58657 | 1-ethyl-1H-imidazole-2-carbaldehyde | C6H8N2O | 详情 | 详情 | |
| (II) | 21674 | 1H-pyrrole | 109-97-7 | C4H5N | 详情 | 详情 |
| (III) | 58658 | 2,7,12,17-tetrakis(1-ethyl-1H-imidazol-2-yl)-21,22,23,24-tetraazapentacyclo[16.2.1.1~3,6~.1~8,11~.1~13,16~]tetracosa-1,3,5,7,9,11(23),12,14,16,18(21),19-undecaene | C40H38N12 | 详情 | 详情 | |
| (IV) | 58659 | 1,3-diethyl-2-[7,12,17-tris(1,3-diethyl-1H-imidazol-3-ium-2-yl)-21,22,23,24-tetraazapentacyclo[16.2.1.1~3,6~.1~8,11~.1~13,16~]tetracosa-1,3,5,7,9,11(23),12,14,16,18(21),19-undecaen-2-yl]-1H-imidazol-3-ium tetraiodide | C48H58I4N12 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(VII)Dilithiation of thiophene (I) employing an excess of BuLi in the presence of TMEDA produced the intermediate 2,5-dilithiothiophene (II). Addition of 4-fluorobenzaldehyde (III) to the organolithium compound (II) afforded the bis-carbinol adduct (IV). Alternatively, addition of benzaldehyde (V) to (II) provided adduct (VI). Boron trifluoride-catalyzed condensation of pyrrole (VII) with diol (IV) yielded the bis(alpha-pyrrolylbenzyl)thiophene (VIII). The dithiaporphyrin derivative (IX) was then obtained by condensation between (VIII) and (VI) in the presence of boron trifluoride. Finally, aromatic sulfonation of (IX) with hot sulfuric acid, followed by neutralization with NaOH furnished the title disulfonate disodium salt.
| 【1】 Hilmey, D.G.; et al.; Water-soluble, core-modified porphyrins as novel longer-wavelength-absorbing sensitizers for photodynamic therapy. II. Effects of core heteroatoms and meso-substituents on biological activity. J Med Chem 2002, 45, 2, 449. |
| 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) | 13297 | Thiophene | 110-02-1 | C4H4S | 详情 | 详情 |
| (II) | 54835 | C4H2Li2S | 详情 | 详情 | ||
| (III) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (IV) | 54836 | (4-fluorophenyl){5-[(4-fluorophenyl)(hydroxy)methyl]-2-thienyl}methanol | C18H14F2O2S | 详情 | 详情 | |
| (V) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (VI) | 54837 | {5-[hydroxy(phenyl)methyl]-2-thienyl}(phenyl)methanol | C18H16O2S | 详情 | 详情 | |
| (VII) | 21674 | 1H-pyrrole | 109-97-7 | C4H5N | 详情 | 详情 |
| (VIII) | 54838 | 2-((4-fluorophenyl){5-[(4-fluorophenyl)(1H-pyrrol-2-yl)methyl]-2-thienyl}methyl)-1H-pyrrole | C26H20F2N2S | 详情 | 详情 | |
| (IX) | 54839 | 7,12-bis(4-fluorophenyl)-2,17-diphenyl-21,23-dithia-22,24-diazapentacyclo[16.2.1.1~3,6~.1~8,11~.1~13,16~]tetracosa-1,3(24),4,6,8,10,12,14,16(22),17,19-undecaene | C44H26F2N2S2 | 详情 | 详情 |