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【结 构 式】 
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【分子编号】10145 【品名】2-Nitro-1H-imidazole; 2-Nitroimidazole 【CA登记号】527-73-1 |
【 分 子 式 】C3H3N3O2 【 分 子 量 】113.07584 【元素组成】C 31.87% H 2.67% N 37.16% O 28.3% |
合成路线1
该中间体在本合成路线中的序号：(I)[2H]-Labeled RSU-1069 is synthesized as follows: The condensation of 2-nitroimidazole (I) with 3-chloro-1,2-epoxypropane (II) gives 1-(3-chloro-2-hydroxypropyl)-2-nitroimidazole (III), which is oxidized with CrO3 - H2SO4 in acetone yielding 1-(3-chloro-2-oxopropyl)-2-nitroimidazole (IV). The reduction of (IV) with NaB[2H]4 in ethanol affords 1-(3-chloro-2-hydroxy-2(2H)-propyl)-2-nitroimidazole (V), which is cyclized with NaOH to the corresponding labeled epoxide (VI). Finally, this compound is condensed with aziridine (VII) by means of triethylamine in refluxing ethanol.
| 【1】 Webb, P.; Threadgill, M.D.; Labelled compounds of interest as antitumour agents. Part II (1). Synthesis of 2H and 3H isotopomers of RSU 1069 and Ro 03-8799 (pimonidazole). J Label Compd Radiopharm 1990, 28, 3, 257. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III),(V) | 10147 | 1-Chloro-3-(2-nitro-1H-imidazol-1-yl)-2-propanol | C6H8ClN3O3 | 详情 | 详情 | |
| (I) | 10145 | 2-Nitro-1H-imidazole; 2-Nitroimidazole | 527-73-1 | C3H3N3O2 | 详情 | 详情 |
| (II) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (IV) | 10148 | 1-Chloro-3-(2-nitro-1H-imidazol-1-yl)acetone | C6H6ClN3O3 | 详情 | 详情 | |
| (V) | 44588 | 1-chloro-3-(2-nitro-1H-imidazol-1-yl)-2-propanol | C6H8ClN3O3 | 详情 | 详情 | |
| (VI) | 10150 | 2-Nitro-1-(2-oxiranylmethyl)-1H-imidazole | C6H7N3O3 | 详情 | 详情 | |
| (VI) | 44589 | 2-nitro-1-(2-oxiranylmethyl)-1H-imidazole | C6H7N3O3 | 详情 | 详情 | |
| (VII) | 10151 | Ethyleneimine; Aziridine; Azirane | 151-56-4 | C2H5N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)[2H]-Labeled pimonidazole is synthesized as follows: The condensation of 2-nitroimidazole (I) with 3-chloro-1,2-epoxypropane (II) gives 1-(3-chloro-2-hydroxypropyl)-2-nitroimidazole (III), which is oxidized with CrO3 - H2SO4 in acetone yielding 1-(3-chloro-2-oxopropyl)-2-nitroimidazole (IV). The reduction of (IV) with NaB[2H]4 in ethanol affords 1-(3-chloro-2-hydroxy-2(2H)-propyl)-2-nitroimidazole (V), which is cyclized with NaOH to the corresponding labeled epoxide (VI). Finally, this compound is condensed with piperidine (VII) in refluxing ethanol.
| 【1】 Webb, P.; Threadgill, M.D.; Labelled compounds of interest as antitumour agents. Part II (1). Synthesis of 2H and 3H isotopomers of RSU 1069 and Ro 03-8799 (pimonidazole). J Label Compd Radiopharm 1990, 28, 3, 257. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III),(V) | 10147 | 1-Chloro-3-(2-nitro-1H-imidazol-1-yl)-2-propanol | C6H8ClN3O3 | 详情 | 详情 | |
| (I) | 10145 | 2-Nitro-1H-imidazole; 2-Nitroimidazole | 527-73-1 | C3H3N3O2 | 详情 | 详情 |
| (II) | 10146 | Epichlorohydrin; 2-(Chloromethyl)oxirane | 106-89-8 | C3H5ClO | 详情 | 详情 |
| (IV) | 10148 | 1-Chloro-3-(2-nitro-1H-imidazol-1-yl)acetone | C6H6ClN3O3 | 详情 | 详情 | |
| (V) | 44588 | 1-chloro-3-(2-nitro-1H-imidazol-1-yl)-2-propanol | C6H8ClN3O3 | 详情 | 详情 | |
| (VI) | 10150 | 2-Nitro-1-(2-oxiranylmethyl)-1H-imidazole | C6H7N3O3 | 详情 | 详情 | |
| (VI) | 44589 | 2-nitro-1-(2-oxiranylmethyl)-1H-imidazole | C6H7N3O3 | 详情 | 详情 | |
| (VII) | 10158 | Piperidine | 110-89-4 | C5H11N | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)1) By condensation of 2-nitroimidazole (I) with 3-(1-piperidino)propyliene oxide (II) in refluxing ethanol.
| 【1】 Grimmelikhuysen, J.; Schroeder, A. (Unilever NV); Preparation of polyacetylalkylenediamines. BE 769655; DE 2133458; FR 2100320; GB 1335204 . |
| 【2】 Castaner, J.; Prous, J.; RO-038799. Drugs Fut 1986, 11, 7, 580. |
合成路线4
该中间体在本合成路线中的序号：(I)The condensation of 2-nitroimidazole (I) with methyl chloroacetate (II) by means of sodium methoxide in hot DMF gives methyl (2-nitro-1-imidazolyl)acetate (III), which is then treated with ethanolamine (IV) in methanol.
| 【1】 Castaner, J.; Robinson, C.; Etanidazole. Drugs Fut 1995, 20, 8, 772. |
| 【2】 Lee, W.W.; Brown, J.M.; Martinez, A.P.; Cory, M.J. (US Department of Health & Human Services); Nitroimidazoles of low toxicity and high activity as radiosensitizers of hypoxic tumor cells. US 4371540 . |
| 【3】 Beaman, A.G.; Duschinsky, R.; Tautz, W.P. (F. Hoffmann-La Roche AG); 2-Nitroimidazoles. US 3679698 . |
| 【4】 Beaman, A.G.; Duschinsky, R.; Tautz, W.P. (F. Hoffmann-La Roche AG); Novel imidazole derivs. and a process for the manufacture thereof. GB 1138529 . |
| 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) | 10145 | 2-Nitro-1H-imidazole; 2-Nitroimidazole | 527-73-1 | C3H3N3O2 | 详情 | 详情 |
| (II) | 10257 | methyl 2-chloroacetate; methyl chloroacetate | 96-34-4 | C3H5ClO2 | 详情 | 详情 |
| (III) | 10258 | methyl 2-(2-nitro-1H-imidazol-1-yl)acetate; Methyl 2-nitro-1-imidazoleacetate | 22813-31-6 | C6H7N3O4 | 详情 | 详情 |
| (IV) | 10259 | Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol | 141-43-5 | C2H7NO | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(V)The acetylation of meso-erythritol (I) with 3 equivalents of Ac2O in pyridine gives 1,3,4-triacetoxy-meso-erythritol (II) with some tetraacetoxy derivative that is separated by chromatography. The reaction of (II) with P2O5 and dimethoxyethane yields 1,3,4-triacetoxy-2-(methoxymethoxy)butane (III), which is treated with Ac2O and BF3/Et2O to afford 1,3,4-triacetoxy-2-(acetoxymethoxy)butane (IV). The condensation of (IV) with 2-nitroimidazole (V) by means of Ts-OH at 130 C or by means of hot N,N-bis(trimethylsilyl)acetamide (BSA) provides the precursor (VI), which is finally deacetylated by means of EtONa in ethanol or TEA in aqueous methanol to furnish the target trihydroxy derivative.
| 【1】 Suzuki, T.; Sakaguchi, M.; Miyata, Y.; Suzuki, A.; Mori, T. (Pola Chemical Industries Inc.); 2-Nitroimidazole deriv., production thereof, and radiosensitizer containing the same as active ingredient. EP 0513351; JP 1991223258; US 5270330; WO 9111440 . |
| 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) | 54252 | (2R,3S)-1,2,3,4-butanetetrol | 149-32-6 | C4H10O4 | 详情 | 详情 |
| (II) | 54253 | (1R,2S)-3-(acetyloxy)-1-[(acetyloxy)methyl]-2-hydroxypropyl acetate | n/a | C10H16O7 | 详情 | 详情 |
| (III) | 54254 | (1R,2S)-3-(acetyloxy)-1-[(acetyloxy)methyl]-2-(methoxymethoxy)propyl acetate | n/a | C12H20O8 | 详情 | 详情 |
| (IV) | 54255 | (1R,2S)-3-(acetyloxy)-2-[(acetyloxy)methoxy]-1-[(acetyloxy)methyl]propyl acetate | n/a | C13H20O9 | 详情 | 详情 |
| (V) | 10145 | 2-Nitro-1H-imidazole; 2-Nitroimidazole | 527-73-1 | C3H3N3O2 | 详情 | 详情 |
| (VI) | 54256 | (1R,2S)-3-(acetyloxy)-1-[(acetyloxy)methyl]-2-[(2-nitro-1H-imidazol-1-yl)methoxy]propyl acetate | n/a | C14H19N3O9 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(I)The condensation of 2-nitroimidazole (I) with N-(3-bromopropyl)phthalimide (II) by means of NaH in DMSO gives N-[3-(2-nitroimidazol-1-yl)propyl]phthalimide (III), which is treated with hydrazine in ethanol/water to yield 3-(2-nitroimidazol-1-yl)propylamine (IV). Finally this amine is condensed with 9-chloroacridine by means of TEA.
| 【1】 Bloomer, W.D.; Papadopoulou, M.V.; Nitroheterocyclic-linked acridines as DNA-targeting bioreductive agents. Drugs Fut 1993, 18, 3, 231. |
| 【2】 DeCarneri, I.; Giraldi, P.N.; Mariotti, V.; Studies on antiprotozoans. Synthesis and biological activity of some styrylimidazole derivatives. J Med Chem 1968, 11, 60-70. |
| 【3】 Adams, G.E.; Ahmed, I.; Stratford, I.J. (Gerald Edward Adams; Ian James Stratford; Israr Ahmed); Bis(nitro-1-imidazolyl alkylamine) platinum complexes useful in radiotheraphy or chemotherapy. GB 2131020 . |
| 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) | 10145 | 2-Nitro-1H-imidazole; 2-Nitroimidazole | 527-73-1 | C3H3N3O2 | 详情 | 详情 |
| (II) | 15216 | N-(3-Bromopropyl)phthalimide; 2-(3-bromopropyl)-1H-isoindole-1,3(2H)-dione | 5460-29-7 | C11H10BrNO2 | 详情 | 详情 |
| (III) | 41281 | 2-[3-(2-nitro-1H-imidazol-1-yl)propyl]-1H-isoindole-1,3(2H)-dione | C14H12N4O4 | 详情 | 详情 | |
| (IV) | 41282 | 3-(2-nitro-1H-imidazol-1-yl)-1-propanamine; 3-(2-nitro-1H-imidazol-1-yl)propylamine | C6H10N4O2 | 详情 | 详情 | |
| (V) | 32672 | 9-chloroacridine | 1207-69-8 | C13H8ClN | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(I)The condensation of 2-nitroimidazole (I) with N-(2-bromoethyl)phthalimide (II) by means of NaH in DMSO gives N-[2-(2-nitroimidazol-1-yl)ethyl]phthalimide (III), which is treated with hydrazine in ethanol/water to yield 2-(2-nitroimidazol-1-yl)ethylamine (IV). Finally this amine is condensed with 9-chloroacridine by means of TEA.
| 【1】 Bloomer, W.D.; Papadopoulou, M.V.; Nitroheterocyclic-linked acridines as DNA-targeting bioreductive agents. Drugs Fut 1993, 18, 3, 231. |
| 【2】 DeCarneri, I.; Giraldi, P.N.; Mariotti, V.; Studies on antiprotozoans. Synthesis and biological activity of some styrylimidazole derivatives. J Med Chem 1968, 11, 60-70. |
| 【3】 Adams, G.E.; Ahmed, I.; Stratford, I.J. (Gerald Edward Adams; Ian James Stratford; Israr Ahmed); Bis(nitro-1-imidazolyl alkylamine) platinum complexes useful in radiotheraphy or chemotherapy. GB 2131020 . |
| 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) | 10145 | 2-Nitro-1H-imidazole; 2-Nitroimidazole | 527-73-1 | C3H3N3O2 | 详情 | 详情 |
| (II) | 37025 | 2-(2-bromoethyl)-1H-isoindole-1,3(2H)-dione | 574-98-1 | C10H8BrNO2 | 详情 | 详情 |
| (III) | 41283 | 2-[2-(2-nitro-1H-imidazol-1-yl)ethyl]-1H-isoindole-1,3(2H)-dione | C13H10N4O4 | 详情 | 详情 | |
| (IV) | 41284 | 2-(2-nitro-1H-imidazol-1-yl)ethylamine; 2-(2-nitro-1H-imidazol-1-yl)-1-ethanamine | C5H8N4O2 | 详情 | 详情 | |
| (V) | 32672 | 9-chloroacridine | 1207-69-8 | C13H8ClN | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(I)The intermediate mixed anhydride (V) has been obtained as follows: the condensation of 2-nitroimidazole (I) with methyl 2-bromoacetate (II) by means of NaOMe in methanol gives 2-(2-nitro-1H-imidazol-1-yl)acetic acid methyl ester (III), which is hydrolyzed with NaOH to yield the corresponding acid (IV). Finally, this compound is condensed with isobutyl chloroformate by means of NMM in THF to afford the desired mixed anhydride intermediate (V). The condensation of 2,2,2-trifluoroacetaldehyde ethyl hemiacetal (VI) with nitromethane (VII) by means of K2CO3 gives 1,1,1-trifluoro-3-nitro-2-propanol (VIII), which is reduced with H2 over RaNi in ethanol to yield 3-amino-1,1,1-trifluoro-2-propanol (IX). Finally, this compound is condensed with the mixed anhydride intermediate (V) by means of NMM in THF to afford the target amide.
| 【1】 Tracy, M.; Kelson, A.B.; Workman, P.; Lewis, A.D.; Aboagye, E.O. (Cancer Research UK; SRI International); Fluorinated 2-nitroimidazole analogs for detecting hypoxic tumor cells. EP 0775117; JP 1998506104; US 5721265; WO 9604249 . |
| 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) | 10145 | 2-Nitro-1H-imidazole; 2-Nitroimidazole | 527-73-1 | C3H3N3O2 | 详情 | 详情 |
| (II) | 12309 | methyl 2-bromoacetate; methyl bromoacetate | 96-32-2 | C3H5BrO2 | 详情 | 详情 |
| (III) | 10258 | methyl 2-(2-nitro-1H-imidazol-1-yl)acetate; Methyl 2-nitro-1-imidazoleacetate | 22813-31-6 | C6H7N3O4 | 详情 | 详情 |
| (IV) | 56733 | 2-(2-nitro-1H-imidazol-1-yl)acetic acid | C5H5N3O4 | 详情 | 详情 | |
| (V) | 56734 | C10H13N3O6 | 详情 | 详情 | ||
| (VI) | 26582 | 1-ethoxy-2,2,2-trifluoro-1-ethanol | 433-27-2 | C4H7F3O2 | 详情 | 详情 |
| (VII) | 39563 | nitromethane | 75-52-5 | CH3NO2 | 详情 | 详情 |
| (VIII) | 56735 | 1,1,1-trifluoro-3-nitro-2-propanol | C3H4F3NO3 | 详情 | 详情 | |
| (IX) | 56736 | 3-amino-1,1,1-trifluoro-2-propanol | 431-38-9 | C3H6F3NO | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(I)The condensation of 2-nitroimidazole (I) with methyl chloroacetate (II) by means of sodium methoxide in methanol - DMF at 150 C gives methyl 2-nitro-1-imidazolylacetate (III), which is then condensed with benzylamine (IV) in methanol.
| 【1】 Castaner, J.; Roberts, P.J.; Benznidazole. Drugs Fut 1977, 2, 9, 568. |
| 【2】 Beaman, A.G.; Duschinsky, R.; Tautz, W.P. (F. Hoffmann-La Roche AG); Novel imidazole derivs. and a process for the manufacture thereof. GB 1138529 . |
| 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) | 10145 | 2-Nitro-1H-imidazole; 2-Nitroimidazole | 527-73-1 | C3H3N3O2 | 详情 | 详情 |
| (II) | 10257 | methyl 2-chloroacetate; methyl chloroacetate | 96-34-4 | C3H5ClO2 | 详情 | 详情 |
| (III) | 10258 | methyl 2-(2-nitro-1H-imidazol-1-yl)acetate; Methyl 2-nitro-1-imidazoleacetate | 22813-31-6 | C6H7N3O4 | 详情 | 详情 |
| (IV) | 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 详情 | 详情 |