|
【结 构 式】 
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【分子编号】11237 【品名】1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate 【CA登记号】1943-83-5 |
【 分 子 式 】C3H4ClNO 【 分 子 量 】105.5236 【元素组成】C 34.15% H 3.82% Cl 33.6% N 13.27% O 15.16% |
合成路线1
该中间体在本合成路线中的序号：(I)The addition of dicyclopropylmethylamine (II) to B-chloroethyl isocyanate (I) in THF gives N-(dicyclopropylmethyl)-N'-(Beta-chloroethyl)urea (III), which is then cyclized in refluxing water.
| 【1】 Malen, C.; Desnos, M.; Laubie, M.; Poignant, J.C. (Servier Laboratoires); Cyclopropylamines as pharmaceuticals. DE 2362754; ES 421879; FR 2212143; GB 1453703; JP 50004084; JP 53056664; JP 53056665 . |
| 【2】 Castaner, J.; Prous, J.; S-3341. Drugs Fut 1986, 11, 6, 470. |
合成路线2
该中间体在本合成路线中的序号：(V)The esterification of N2-(benzyloxycarbonyl)-D,L-glutamine (I) with methyl iodide and KHCO3 in DMF gives the corresponding methyl ester (II), which is cyclized to benzyl D,L-2,6-dioxo-3-piperidinecarbamate (III) by heating. The hydrogenolysis of (III) with H2 over Pd/C in methanol yields D,L-2-aminoglutarimide (IV), which is condensed with 2-chloroethyl isocyanate (V) in DMF affording 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl)urea (VI). Finally, this compound is nitrosated in the usual way with NaNO2 in formic acid.
| 【1】 Johnston, T.P.; et al.; The synthesis of potential anticancer agents. XXXVI. N-Nitrosoureas. II. Haloalkyl derivatives. J Med Chem 1966, 9, 6, 892-911. |
| 【2】 Woodman, R.J.; Castaner, J.; PCNU. Drugs Fut 1981, 6, 8, 481. |
| 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) | 37578 | N(2)-[(benzyloxy)carbonyl]glutamine | C13H16N2O5 | 详情 | 详情 | |
| (II) | 37579 | methyl 5-amino-2-[[(benzyloxy)carbonyl]amino]-5-oxopentanoate | C14H18N2O5 | 详情 | 详情 | |
| (III) | 37575 | benzyl 2,6-dioxo-3-piperidinylcarbamate | C13H14N2O4 | 详情 | 详情 | |
| (IV) | 37576 | 3-amino-2,6-piperidinedione；3-aminopiperidine-2,6-dione；2-amino-Glutarimide；Glutamimide;a-Aminoglutarimide | 2353-44-8 | C5H8N2O2 | 详情 | 详情 |
| (V) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (VI) | 37577 | N-(2-chloroethyl)-N'-(2,6-dioxo-3-piperidinyl)urea | C8H12ClN3O3 | 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 condensation of 1-oxyl-2,2,6,6-tetramethyl-4-aminopiperidine (I) with 2-chloroethyl isocyanate (II) gives 1-(2-chloroethyl)-3-(1-oxyl-2,2,6,6-tetramethylpiperidinyl)urea (III). The nitrosation of (III) with dinitrogen tetraoxide in methylene chloride yields SLCNU.
| 【1】 Arai, Y.; Takeda, M.; Tsujihara, K.; Morikawa, T.; A new class of nitrosoureas. VII. Synthesis and antitumor activity of 3-substituted 1-(2-chloroethyl)-3-(methyl-alpha-D-glucopyranosid-3-yl)-1-nitrosoureas. Chem Pharm Bull 1982, 30, 4365. |
| 【2】 Li, S.W.; Sosnovsky, G.; SLCNU. Drugs Fut 1985, 10, 3, 211. |
| 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) | 14610 | 4-Amino-TEMPO; 4-amino-2,2,6,6-tetramethyltetrahydro-1(2H)-pyridinol | 14691-88-4 | C9H19N2O | 详情 | 详情 |
| (II) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (III) | 29078 | N-(2-chloroethyl)-N'-(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)urea | C12H23ClN3O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(IV)The reaction of maltose (I) with isobutylamine (II) in methanol at 65 C gives isobutylmaltosylamine (III), which is condensed with 2-chloroethyl isocyanate (IV) yielding 1-(2-chloroethyl)-3-isobutyl-3-D-maltosylurea (V). The nitrosation of (V) with dinitrogen tetroxide in THF in the presence of sodium acetate gives 1-(2-chloroethyl)-3-isobutyl-3-(beta-D-heptanitrosomaltosyl)-1-nitrosourea (VI). The nitrous esters of (VI) can be decomposed without affecting the N-nitroso group by addition of methanol under acidic conditions to give TA-077 in good yield.
| 【1】 Arai, Y.; Ozeki, M.; Morikawa, T.; Umino, N.; Kawamori, M.; Tsujihara, K.; A new class of nitrosoureas. III. Synthesis and antitumor activity of 3,3-disubstituted-1(2-chloroethyl)-1-nitrosoureas having a arabinopyranosyl, xylopyranosyl or ribopyranosyl moiety. Chem Pharm Bull 1982, 30, 534-543. |
| 【2】 Taga, M.; Morikawa, T.; Kawamori, M.; Ozeki, M.; Arai, Y.; Tsujihara, K.; Miyazaki, M.; A new class of nitrosoureas. II. Synthesis and antitumor activity of 1-(2-chloroehtyl)-3,3-disubstituted-1-nitrosoureas having a glucopyranosyl, mannopyranosyl or galactopyranosyl moiety. Chem Pharm Bull 1981, 29, 3262. |
| 【3】 Tsujihara, K.; Ozeki, M.; Arai, Y.; Morikawa, T.; Akaike, Y.; Kawamori, M.; A new class of nitrosoureas. 4. Synthesis and antitumor activity of disaccharide derivatives of 3,3-disubstituted 1-(2-chloroethyl)-1-nitrosoureas. J Med Chem 1982, 25, 4, 441-446. |
| 【4】 Fujimoto, S.; Ogawa, M.; TA-077. Drugs Fut 1984, 9, 2, 126. |
| 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) | 29998 | (3R,4R,5S,6R)-6-(hydroxymethyl)-5-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]tetrahydro-2H-pyran-2,3,4-triol; Maltose | 9005-84-9 | C12H22O11 | 详情 | 详情 |
| (II) | 13306 | 2-Methyl-1-propanamine; Isobutylamine | 78-81-9 | C4H11N | 详情 | 详情 |
| (III) | 29999 | (2R,3R,4S,5S,6R)-2-[[(2R,3S,4R,5R,6R)-4,5-dihydroxy-2-(hydroxymethyl)-6-(isobutylamino)tetrahydro-2H-pyran-3-yl]oxy]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; Isobutylmaltosylamine | C16H31NO10 | 详情 | 详情 | |
| (IV) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (V) | 30000 | N'-(2-Chloroethyl)-N-((2R,3R,4R,5S,6R)-3,4-dihydroxy-6-(hydroxymethyl)-5-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]tetrahydro-2H-pyran-2-yl)-N-isobutylurea; 1-(2-Chloroethyl)-3-isobutyl-3-D-maltosylurea | C19H35ClN2O11 | 详情 | 详情 | |
| (VI) | 30001 | (2R,3R,4S,5R,6R)-2-[[(2R,3R,4S,5R,6R)-6-[[[1-(2-chloroethyl)-2-oxohydrazino]carbonyl](isobutyl)amino]-4,5-dinitrosooxy-2-(nitrosooxymethyl)tetrahydro-2H-pyran-3-yl]oxy]-3,5-dinitrosooxy-6-(nitrosooxymethyl)tetrahydro-2H-pyran-4-yl nitrite; 1-(2-Chloroethyl)-3-isobutyl-3-(beta-D-heptanitrosomaltosyl)-1-nitrosourea | C19H27ClN10O19 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)By cyclization of 5-diazoimidazole-4-carboxamide (I) with 2-chloroethyl isocyanate (II) in dichloromethane.
| 【1】 Gibson, N.W.; Hickman, J.A.; The role of isocyanates in the toxicity of antitumor haloalkylnitrosoureas. Biochem Pharmacol 1982, 31, 17, 2795-2800. |
| 【2】 Lunt, E.; Stevens, M.F.G.; Stone, R.; Woolbridge, K.R.H. (Cancer Research Campaign Technology Ltd.); Tetrazine derivs., process for their preparation and pharmaceutical compsns. containing them. BE 894175; DE 3231255; FR 2511679; GB 2104522; JP 1983043975; US 5260291 . |
| 【3】 Hopkins, S.J.; Serradell, M.N.; Castaner, J.; Mitozolomide. Drugs Fut 1984, 9, 11, 827. |
| 【4】 Stevens, M.F.G.; Hickman, J.A.; Stone, R.; Gibson, N.W.; Baig, G.U.; Lunt, E.; Newton, C.G.; Antitumor imidazotetrazinones. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one, a novel broad-spectrum antitumor agent. J Med Chem 1984, 27, 196-201, 196. |
合成路线6
该中间体在本合成路线中的序号：(II)The reaction of vinblastine (I) with 2-chloroethyl isocyanate (II) in refluxing benzene gives the corresponding N-(2-chloroethyl)carbamate (III), which is cyclized by continuous refluxing in the same solvent.
| 【1】 Miller, J.C.; Gutowski, G.E.; Oxazolidinedione derivatives of Vinca alkaloids. FR 2372839; GB 1590649; JP 53071100; US 4096148 . |
| 【2】 Hopkins, S.J.; Vinzolidine Sulfate. Drugs Fut 1984, 9, 12, 913. |
| 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) | 10346 | methyl (3aR,4R,5S,5aR,10bR,13aR)-4-(acetoxy)-3a-ethyl-9-[(13S,15S,17S)-17-ethyl-17-hydroxy-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0(4,12).0(5,10)]nonadeca-4(12),5,7,9-tetraen-13-yl]-5-hydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate | 446-86-6 | C46H58N4O9 | 详情 | 详情 |
| (II) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (III) | 34248 | C49H62ClN5O10 | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(I)HECNU can be prepared as follows (2): The reaction of 2-chloroethylisocyanate (I) with activated sodium azide yields 2-chloroethylcarbamoylazide (II). The preparation of N-(2-chloroethyl)-N-nitrosocarbamoylazide (III) was performed by adding 2-chloroethylcarbamoyiazide (III) to a suspension of anhydrous sodium acetate and nitrogen tetroxide in carbon tetrachloride. Reaction of N-(2-chloroethyl)-N-nitrosocarbamoylazide (III) with ethanolamine (IV) in isopropanol yields elmustine. The described synthetic approach offers a useful means to get the nitroso group attached to the required position.
| 【1】 Eisenbrand, G.; et al.; Some new congeners of the anticancer 1,2-bis(2-chloroethyl)-1-nitrosourea (BCNU). Synthesis of bifunctional analogs and water soluble derivatives and preliminary evaluation of their chemotherapeutic potential. Z Krebsforsch 1976, 86, 279. |
| 【2】 Hansch, C.; et al.; Quantitative structure activity relationships of antineoplastic drugs: Nitrosoureas and triazenoimidazoles. Cancer Chemother Rep 1972, 56, 443. |
| 【3】 Castaner, J.; Serradell, M.N.; Elmustine. Drugs Fut 1984, 9, 1, 18. |
| 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) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (II) | 29946 | 1-[(azidocarbonyl)amino]-2-chloroethane | C3H5ClN4O | 详情 | 详情 | |
| (III) | 24460 | 1-(2-chloroethyl)-2-oxo-1-hydrazinecarbonyl azide | C3H4ClN5O2 | 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8
该中间体在本合成路线中的序号：(III)2) The condensation of compound (I) with 2-chloroethyl isocyanate (III) by means of silver carbonate in acetonitrile water gives methyl 6-[[-(2-chloroethyl) amino]carbonylamino]-6-deoxy-alpha-D-glucopyranoside (IV), which is then nitrosated with NaNO2 in aqueous acetic acid
| 【1】 Kimura, G.; Sekine, J. (Tokyo Tanabe Co., Ltd.); Alkyl amino-glucopyranoside derivative and process for producing the same. CA 1044228; CH 610334; DE 2530416; FR 2276828; GB 1499760; JP 7606925; JP 77125126; JP 7797915; NL 7507973 . |
| 【2】 Prous, J.; Castaner, J.; Ranimustine. Drugs Fut 1986, 11, 9, 762. |
| 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) | 24328 | (2R,3S,4S,5R,6S)-2-(aminomethyl)-6-methoxytetrahydro-2H-pyran-3,4,5-triol | C7H15NO5 | 详情 | 详情 | |
| (III) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (IV) | 24332 | N-(2-chloroethyl)-N'-[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-methoxytetrahydro-2H-pyran-2-yl]methyl]urea | C10H19ClN2O6 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(II)1) N,N-Dimethyl-2-aminoethanesulfonamide (I) is condensed with 2-chloroethyl isocyanate (II) by means of triethylamine in CHCl3 giving 1-(2-chloroethyl)- isocyanate (II) by means of triethylamine in CHCl3 giving 1-(2-chloroethyl)-3-[2-(dimethylsulfamoyl)ethyl]urea (III), which is nitrosated with NaNO3, N2O4 or NOCl in acetic acid-acetic anhydride.
| 【1】 Carlsson, J.-I.; Jensen, P.H.G.; Stamvik, A.R. (Leo Pharma AB); N-nitroso compounds and compositions containing such compounds. EP 0106123; JP 59073562; US 4613695 . |
| 【2】 Prous, J.; Castaner, J.; Tauromustine. Drugs Fut 1986, 11, 7, 585. |
合成路线10
该中间体在本合成路线中的序号：(II)The reaction of 4-nitrophenol (I) with 2-chloroethyl isocyanate (II) in pyridine leads to the activated carbamate (III), which is nitrosated by reacting with nitrosyl chloride in pyridine at -20 C to yield 4-nitrophenyl N-(2-chloroethyl)-N-nitrosocarbamate (IV). The nitrosated molecule (IV) is reacted with 2-(methylthio)ethylamine (V) in THF at ordinary temperature affording the sulfure urea (VI), which is then oxidized to the sulfonyl compound (VII) by hydrogen peroxide in formic acid at 50 C.
| 【1】 Godeneche, D.; Imbach, J.-L.; Madelmont, J.-C.; Meyniel, G.; Moreau, M.-F.; Oiry, J.; Parry, D. (CNRS (Centre National de la Recherche Scientifique); INSERM (Institut National de la Sante et de la Recherche Medicale)); Novel nitrosourea cpds. Process of preparation. Compsns. based on these cpds. useful in anticancer chemotherapy. EP 0185020; FR 2562890; JP 1988502269; WO 8504655 . |
| 【2】 Madelmont, J.-C.; Godeneche, D.; Moreau, M.-F.; Parry, D.; Meyniel, G.; Oiry, J.; Imbach, J.-L. (CNRS (Centre National de la Recherche Scientifique); INSERM (Institut National de la Sante et de la Recherche Medicale)); Nitrosoureas compounds, preparation thereof and utilization thereof in anticancerous. US 5001158 . |
| 【3】 Meyniel, G.; Duprat, J.; Mathe, G.; Plagne, R.; Godeneche, D.; Parry, D.; Madelmont, J.C.; Chabard, J.L.; New cysteamin(2-chloroethyl)nitrosoureas. Synthesis and preliminary antitumor results. J Med Chem 1985, 28, 9, 1346-50. |
| 【4】 Madelmont, J.C.; Cystemustine. Drugs Fut 1994, 19, 1, 27. |
| 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) | 11236 | 4-Nitrophenol; p-Nitrophenol | 100-02-7 | C6H5NO3 | 详情 | 详情 |
| (II) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (III) | 11238 | 4-nitrophenyl N-(2-chloroethyl)carbamate | C9H9ClN2O4 | 详情 | 详情 | |
| (IV) | 11239 | 4-nitrophenyl 1-(2-chloroethyl)-2-oxo-1-hydrazinecarboxylate | C9H8ClN3O5 | 详情 | 详情 | |
| (V) | 11240 | 2-(Methylsulfanyl)ethylamine; 2-(Methylthio)ethylamine; 2-(Methylsulfanyl)-1-ethanamine | 18542-42-2 | C3H9NS | 详情 | 详情 |
| (VI) | 11241 | 1-(2-Chloroethyl)-N-[2-(methylsulfanyl)ethyl]-2-oxo-1-hydrazinecarboxamide | C6H12ClN3O2S | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(II)The pyrazolo[5,1-d]-1,2,3,5-tetrazine ring is synthesized according to the general method of Ege and Gilbert by the condensation of 3-diazopyrazole-4-carboxamide (I) with 2-chloroethyl isocyanate (II) in ethyl acetate at room temperature, followed by heating the reaction mixture at 50-60 C. The product may be purified through a silica gel column using ethyl acetate as the eluent. In contrast to the preparation of mitozolomide, the entire operation, including the preparation of the starting 3-diazo derivative, can be conducted under ordinary laboratory illumination. The dry product is stable under light even after 6 months.
| 【1】 Zolopa, A.R.; Whitcomb, J.M.; Hughes, M.D.; Katzenstein, D.A.; Winters, M.S.; Shafer, R.W.; Bates, M.; Shulman, N.S.; Hellmann, N.S.; J Pharm Sci 1968, 57, 2, 1044-1045. |
| 【2】 Roberts, M.S.; Smith, K.J.; Tetrahedron Lett 1979, 113, 4, 4235-4256. |
| 【3】 Cheng, C.C. (Pfizer Inc.); 3-(Haloethyl)-4-oxopyrazolo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide compounds. JP 60011489; US 4504475 . |
| 【4】 Zee-Cheng, R.K.-Y.; Cheng, C.C.; Pyraoncozine. Drugs Fut 1986, 11, 2, 121. |
合成路线12
该中间体在本合成路线中的序号：(II)The compound can be prepared by reacting mercaptopurine (I) with 2-chloroethylisocyanate (II) in an inert medium at a temperature from 0-50 C, preferably in the presence of an alkaline agent. Suitable inert media for the reaction are dimethylformamide, dimethylsulfoxide, phosphoric acid, hexamethyltriamide or tetramethylurea. Alkaline agents, preferably tertiary organic amines, accelerate the reaction and make the yield of the desired product higher.
| 【1】 Cerny, A.; Krepelka, J.I.; Melka, M.; Molko, M.; Pokorná, S.; Reichová, R.; Kejhová, I.; Beitová, M.; Grimová, J. (SPOFA - United Pharmaceutical Works); 6-Purinyl N-(2-chloroethyl)carbamate and thiocarbamate, a process for their preparation and use thereof. CS 249576. EP 0186454; JP 1986186382; US 4720497 . |
| 【2】 Melka, M.; Krepelka, J.; Miko, M.; CLOTURIN. Drugs Fut 1990, 15, 4, 337. |
合成路线13
该中间体在本合成路线中的序号：(I)The condensation of 2-chloroethyl isocyanate (I) with diethyl 1-aminoethylphosphonate (II) in chloroform gives diethyl 1-[3-(2-chloroethyl)ureido]ethylphosphonate (III), which is then treated with sodium nitrite and formic acid.
| 【1】 Lavielle, G.; Cudennec, C. (ADIR et Cie.); New nitrosourea derivs., process for preparing them and pharmaceutical compsns. containing them. FR 2536075 . |
| 【2】 Prous, J.; Castaner, J.; FOTEMUSTINE < Rec INN >. Drugs Fut 1989, 14, 11, 1042. |
合成路线14
该中间体在本合成路线中的序号：(II)The reaction of pyridine-4-amine (I) with 2-chloroethyl isocyanate (II) in toluene gives N-(2-chloroethyl)-N'-(4-pyridyl)urea (III), which is cyclized by means of NaH in DMF/THF, yielding 1-(4-pyridyl)imidazolidin-2-one (IV). Finally, this compound is condensed with 4-(5-bromopentyloxy)biphenyl (V) by means of NaH in DMF to afford the target disubstituted imidazolidinone. (1,2)
| 【1】 Chang, C.-M.; Li, W.-T.; Shia, K.-S.; et al.; Design, synthesis, and structure-activity relationship of pyridyl imidazolidinones: A novel class of potent and selective human enterovirus 71 inhibitors. J Med Chem 2002, 45, 8, 1644. |
| 【2】 Hsu, M.-C.; Li, W.-T.; Chang, C.-M.; Shia, K.-S.; Shih, S.-R.; Chern, J.-H.; Chen, S.-J. (National Health Research Institutes); Imidazolidinone cpds.. US 2003087936; US 6706739 . |
| 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) | 25661 | 4-pyridinamine; 4-aminopyridine | 5044-74-5 | C5H6N2 | 详情 | 详情 |
| (II) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (III) | 53583 | N-(2-chloroethyl)-N'-(4-pyridinyl)urea | 62491-96-7 | C8H10ClN3O | 详情 | 详情 |
| (IV) | 53584 | 1-(4-pyridinyl)-2-imidazolidinone | n/a | C8H9N3O | 详情 | 详情 |
| (V) | 53585 | 4-[(5-bromopentyl)oxy]-1,1'-biphenyl; [1,1'-biphenyl]-4-yl 5-bromopentyl ether | n/a | C17H19BrO | 详情 | 详情 |
合成路线15
该中间体在本合成路线中的序号：(IV)Condensation of 1,8-naphthalic anhydride (I) with ethylenediamine (II) provides the N-aminoethyl naphthalimide (III). Amine (III) is subsequently condensed with 2-chloroethyl isocyanate (IV) to afford urea (V). Finally, nitrosation of (V) by means of NaNO2 and formic acid leads to the title N-nitrosourea.
| 【1】 Samanta, S.; et al.; Evaluation of naphthal-NU, a 2-chloroethylnitrosourea derivative of naphthalimide, as a mixed-function anticancer agent. J Exp Clin Cancer Res 2002, 21, 1, 87. |
| 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) | 16982 | 1H,3H-benzo[de]isochromene-1,3-dione; 1,8-Naphthalic Anhydride | 81-84-5 | C12H6O3 | 详情 | 详情 |
| (II) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |
| (III) | 59030 | 2-(2-aminoethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione | C14H12N2O2 | 详情 | 详情 | |
| (IV) | 11237 | 1-Chloro-2-isocyanatoethane; 2-Chloroethyl isocyanate | 1943-83-5 | C3H4ClNO | 详情 | 详情 |
| (V) | 59031 | N-(2-chloroethyl)-N'-{2-[1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl]ethyl}urea | C17H16ClN3O3 | 详情 | 详情 |