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【结 构 式】

【分子编号】54020

【品名】1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid

【CA登记号】

【 分 子 式 】C10H14N2O4

【 分 子 量 】226.23224

【元素组成】C 53.09% H 6.24% N 12.38% O 28.29%

与该中间体有关的原料药合成路线共 3 条

合成路线1

该中间体在本合成路线中的序号:(II)

The hydrolysis of the 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid ethyl ester (I) with NaOH in hot ethanol gives the carboxylic acid (II), which is treated with refluxing SOCl2 to yield the acyl chloride (III). The reaction of (III) with 3-aminopropionitrile (IV) in toluene affords the carboxamide (V), which is treated with propane-1,3-diamine (VI) and HCl in ethanol to provide the tetrahydropyrimidine derivative (VII). The reduction of the nitro group of (VII) with H2 over Pd/C in methanol gives the aminopyrrole (VIII), which is finally condensed with bis pentafluorophenyl terephthalate (XI) to afford the target terephthalamide. The activated ester bis pentafluorophenyl terephthalate (XI) has been obtained by esterification of terephthalic acid (IX) with pentafluorophenyl trifluoroacetate (X) by means of DIEA in DMF.

1 Roberts, C.D.; Keicher, J.D.; Dyatkina, N.B.; et al.; Minor groove DNA binders as antimicrobial agents. 1. Pyrrole tetraamides are potent antibacterials against vancomycin resistant Enteroccoci and methicillin resistant Staphylococcus aureus. J Med Chem 2002, 45, 4, 805.
2 Nelson, P.H.; Muchowski, J.M.; Dyatkina, N.B.; Shi, D.-F.; Zhang, W.; Liehr, S.J.R.; Velligan, M.D.; Botyanszki, J.; Roberts, C.D.; Khorlin, A. (Genelabs Technologies, Inc.); Novel cpds. possessing antibacterial, antifungal or antitumor activity. WO 0200650 .
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) 54019 ethyl 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylate C12H18N2O4 详情 详情
(II) 54020 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid C10H14N2O4 详情 详情
(III) 54021 1-isopentyl-4-nitro-1H-pyrrole-2-carbonyl chloride C10H13ClN2O3 详情 详情
(IV) 38094 3-aminopropanenitrile 151-18-8 C3H6N2 详情 详情
(V) 54022 N-(2-cyanoethyl)-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide C13H18N4O3 详情 详情
(VI) 19331 3-aminopropylamine; 1,3-propanediamine 109-76-2 C3H10N2 详情 详情
(VII) 54023 1-isopentyl-4-nitro-N-[2-(1,4,5,6-tetrahydro-2-pyrimidinyl)ethyl]-1H-pyrrole-2-carboxamide C16H25N5O3 详情 详情
(VIII) 54024 4-amino-1-isopentyl-N-[2-(1,4,5,6-tetrahydro-2-pyrimidinyl)ethyl]-1H-pyrrole-2-carboxamide C16H27N5O 详情 详情
(IX) 54025 1,4-Benzenedicarboxylic acid; Benzene-1,4-dicarboxylic acid; p-Benzenedicarboxylic acid; p-Phthalic acid; Terephthalic acid 100-21-0 C8H6O4 详情 详情
(X) 54026 Trifluoroacetic acid pentafluorophenylester 14533-84-7 C8F8O2 详情 详情
(XI) 54027 bis(2,3,4,5,6-pentafluorophenyl) terephthalate C20H4F10O4 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

Alkylation of ethyl 4-nitropyrrole-2-carboxylate (I) with 3-methylbutyl bromide (II) in the presence of NaOMe affords the N-isoamyl pyrrole (III). Saponification of the ethyl ester group of (III), followed by treatment of the resultant carboxylic acid (IV) with SOCl2 provides acid chloride (V). This is subsequently coupled with 3-aminopropionitrile (VI) to yield the N-(2-cyanoethyl) amide (VII). Conversion of the cyano group of (VII) into the N-methyl amidine (VIII) is then accomplished under Pinner reaction conditions. Reduction of the nitro group of (VIII) by catalytic hydrogenation over Pd/C furnishes the intermediate aminopyrrole (IX).

1 Roberts, C.D.; Keicher, J.D.; Dyatkina, N.B.; et al.; Minor groove DNA binders as antimicrobial agents. 1. Pyrrole tetraamides are potent antibacterials against vancomycin resistant Enteroccoci and methicillin resistant Staphylococcus aureus. J Med Chem 2002, 45, 4, 805.
2 Dyatkina, N.; Hanson, E.; Liehr, S.; et al.; Synthesis, SAR and antimicrobial activity of pyrrole tetraamides. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 62.
3 Nelson, P.H.; Muchowski, J.M.; Dyatkina, N.B.; Shi, D.-F.; Zhang, W.; Liehr, S.J.R.; Velligan, M.D.; Botyanszki, J.; Roberts, C.D.; Khorlin, A. (Genelabs Technologies, Inc.); Novel cpds. possessing antibacterial, antifungal or antitumor activity. WO 0200650 .
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) 60988 1-methoxy-2,3-dihydro-1H-inden-2-yl methanesulfonate C11H14O4S 详情 详情
(II) 46234 1-bromo-3-methylbutane C5H11Br 详情 详情
(III) 54019 ethyl 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylate C12H18N2O4 详情 详情
(IV) 54020 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid C10H14N2O4 详情 详情
(V) 54021 1-isopentyl-4-nitro-1H-pyrrole-2-carbonyl chloride C10H13ClN2O3 详情 详情
(VI) 38094 3-aminopropanenitrile 151-18-8 C3H6N2 详情 详情
(VII) 54022 N-(2-cyanoethyl)-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide C13H18N4O3 详情 详情
(VIII) 60999 N-[3-imino-3-(methylamino)propyl]-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide C14H23N5O3 详情 详情
(IX) 61000 4-amino-N-[3-imino-3-(methylamino)propyl]-1-isopentyl-1H-pyrrole-2-carboxamide C14H25N5O 详情 详情

合成路线3

该中间体在本合成路线中的序号:(II)

The hydrolysis of the 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid ethyl ester (I) with NaOH in hot ethanol gives the carboxylic acid (II), which is treated with refluxing SOCl2 to yield the acyl chloride (III). The reaction of (III) with 3-aminopropionitrile (IV) in toluene affords the carboxamide (V), which is treated with ethylamine (VI) and HCl in ethanol to provide the N-ethylamidino derivative (VII). The reduction of the nitro group of (VII) with H2 over Pd/C in methanol gives the aminopyrrole (VIII), which is finally condensed with bis pentafluorophenyl terephthalate (XI) to afford the target terephthalamide. The activated ester bis pentafluorophenyl terephthalate (XI) has been obtained by esterification of terephthalic acid (IX) with pentafluorophenyl trifluoroacetate (X) by means of DIEA in DMF.

1 Roberts, C.D.; Keicher, J.D.; Dyatkina, N.B.; et al.; Minor groove DNA binders as antimicrobial agents. 1. Pyrrole tetraamides are potent antibacterials against vancomycin resistant Enteroccoci and methicillin resistant Staphylococcus aureus. J Med Chem 2002, 45, 4, 805.
2 Nelson, P.H.; Muchowski, J.M.; Dyatkina, N.B.; Shi, D.-F.; Zhang, W.; Liehr, S.J.R.; Velligan, M.D.; Botyanszki, J.; Roberts, C.D.; Khorlin, A. (Genelabs Technologies, Inc.); Novel cpds. possessing antibacterial, antifungal or antitumor activity. WO 0200650 .
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) 54019 ethyl 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylate C12H18N2O4 详情 详情
(II) 54020 1-isopentyl-4-nitro-1H-pyrrole-2-carboxylic acid C10H14N2O4 详情 详情
(III) 54021 1-isopentyl-4-nitro-1H-pyrrole-2-carbonyl chloride C10H13ClN2O3 详情 详情
(IV) 38094 3-aminopropanenitrile 151-18-8 C3H6N2 详情 详情
(V) 54022 N-(2-cyanoethyl)-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide C13H18N4O3 详情 详情
(VI) 10928 Ethanamine 75-04-7 C2H7N 详情 详情
(VII) 54028 N-[3-(ethylamino)-3-iminopropyl]-1-isopentyl-4-nitro-1H-pyrrole-2-carboxamide C15H25N5O3 详情 详情
(VIII) 54029 4-amino-N-[3-(ethylamino)-3-iminopropyl]-1-isopentyl-1H-pyrrole-2-carboxamide C15H27N5O 详情 详情
(IX) 54025 1,4-Benzenedicarboxylic acid; Benzene-1,4-dicarboxylic acid; p-Benzenedicarboxylic acid; p-Phthalic acid; Terephthalic acid 100-21-0 C8H6O4 详情 详情
(X) 54026 Trifluoroacetic acid pentafluorophenylester 14533-84-7 C8F8O2 详情 详情
(XI) 54027 bis(2,3,4,5,6-pentafluorophenyl) terephthalate C20H4F10O4 详情 详情
Extended Information