|
【结 构 式】 
|
【分子编号】34400 【品名】1-(4-nitrophenyl)hydrazine; 4-Nitrophenylhydrazine 【CA登记号】100-16-3 |
【 分 子 式 】C6H7N3O2 【 分 子 量 】153.1406 【元素组成】C 47.06% H 4.61% N 27.44% O 20.9% |
合成路线1
该中间体在本合成路线中的序号：(I)The condensation of p-nitrophenylhydrazine (I) with benzazepinedione (II) in AcOH produced hydrazone (III). Subsequent Fischer indole synthesis employing (III) and H2SO4 furnished the title indolobenzazepinone.
| 【1】 Schultz, C.; Zaharevitz, D.W.; Mejer, L.; Gussio, R.; Leost, M.; Sausville, E.A.; Kunick, C.; Link, A.; Paullones, a series of cyclin-dependent kinase inhibitors: Synthesis, evaluation of CDK1/cyclin B inhibition, and in vitro antitumor activity. J Med Chem 1999, 42, 15, 2909. |
合成路线2
该中间体在本合成路线中的序号：(II)Fischer indole cyclization of naltrexone (I) with 4-nitrophenylhydrazine (II) provided 5'-nitronaltrindole (III). Subsequent reduction of the nitro group of (III) by means of hydrazine hydrate and Raney Nickel gave the 5'-amino derivative (IV). Mercury-assisted condensation of (IV) with di(tert-butoxy-carbonyl)thiourea (V) afforded the protected guanidine (VI). Finally, the Boc groups of (VI) were cleaved by treatment with trifluoroacetic acid to furnish the title compound.
| 【1】 Jones, R.M.; Hjorth, S.A.; Schwartz, T.W.; Portoghese, P.S.; Mutational evidence for a common kappa antagonist binding pocket in the wild-type kappa and mutant mu[K303E] opioid receptors. J Med Chem 1998, 41, 25, 4911. |
| 【2】 Sercel, A.D.; Stevens, W.C. Jr.; Ingals, S.; et al.; Naltrindole analogs as potent and selective kappa-opioid receptor antagonists. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 267. |
| 【3】 Stevens, W.C.; Jones, R.M.; Subramanian, G.; Metzger, T.G.; Ferguson, D.M.; Portoghese, P.S.; Potent and selective indolomorphinan antagonists of the kappa-opioid receptor. J Med Chem 2000, 43, 14, 2759. |
| 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) | 25079 | (1S,5R,13R,17S)-4-(cyclopropylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one; Naltrexone | 16590-41-3 | C20H23NO4 | 详情 | 详情 |
| (II) | 34400 | 1-(4-nitrophenyl)hydrazine; 4-Nitrophenylhydrazine | 100-16-3 | C6H7N3O2 | 详情 | 详情 |
| (III) | 34703 | (1S,2S,13R,21R)-22-(cyclopropylmethyl)-7-nitro-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol | C26H25N3O5 | 详情 | 详情 | |
| (IV) | 34704 | (1S,2S,13R,21R)-7-amino-22-(cyclopropylmethyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol | C26H27N3O3 | 详情 | 详情 | |
| (V) | 21843 | tert-butyl [(tert-butoxycarbonyl)amino]carbothioylcarbamate | 145013-05-4 | C11H20N2O4S | 详情 | 详情 |
| (VI) | 34705 | tert-butyl (Z)-[(tert-butoxycarbonyl)amino][[(1S,2S,13R,21R)-22-(cyclopropylmethyl)-2,16-dihydroxy-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaen-7-yl]amino]methylidenecarbamate | C37H45N5O7 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Acid-catalyzed condensation of 4-nitrophenylhydrazine (I) with 1,1,1,5,5,5-hexafluoro-2,4-pentanedione (II) produced pyrazole (III). Reduction of the nitro group of (III) to the corresponding amine (IV) was achieved either by treatment with stannous chloride or by catalytic hydrogenation over Pd/C. Fluoroisonicotinic acid (VI) was prepared by lithiation of 3-fluoropyridine (V) at -78 C followed by quenching with dry ice. Finally, coupling of acid (VI) with amine (IV) yielded the target amide.
| 【1】 Sciotti, R.J.; Wagenaar, F.L.; Zhou, X.; Wiedeman, P.E.; Warrior, U.; Luly, J.R.; Djuric, S.W.; Tu, N.P.; Ba Maung, N.Y.; Madar, D.J.; Gubbins, E.J.; Basha, A. (Abbott Laboratories Inc.); Pyrazole inhibitors of cytokine production. EP 1068187; WO 9951580 . |
| 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) | 34400 | 1-(4-nitrophenyl)hydrazine; 4-Nitrophenylhydrazine | 100-16-3 | C6H7N3O2 | 详情 | 详情 |
| (II) | 50521 | Hexafluoroacetylacetone; 1,1,1,5,5,5-Hexafluoro-2,4-pentanedione; 1,1,1,5,5,5-Hexafluoroacetylacetonate; 1,1,1,5,5,5-Hexafluoroacetylacetone; 1,1,1-Hexafluoro-2,4-pentanedione | 1522-22-1 | C5H2F6O2 | 详情 | 详情 |
| (III) | 50522 | 1-(4-nitrophenyl)-3,5-bis(trifluoromethyl)-1H-pyrazole | C11H5F6N3O2 | 详情 | 详情 | |
| (IV) | 50523 | 4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenylamine; 4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]aniline | C11H7F6N3 | 详情 | 详情 | |
| (V) | 46855 | 3-fluoropyridine | 372-47-4 | C5H4FN | 详情 | 详情 |
| (VI) | 50524 | 3-fluoroisonicotinic acid | C6H4FNO2 | 详情 | 详情 |