8-methyl-5-(4-nitrophenyl)-9H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine -Drug Synthesis Database

【结构式】

【分子编号】29266

【品名】8-methyl-5-(4-nitrophenyl)-9H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine

【CA登记号】

【分子式】C₁₇H₁₃N₃O₄

【分子量】323.30804

【元素组成】C 63.16% H 4.05% N 13% O 19.79%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

The regioselective reduction of 8-methyl-5-(4-nitrophenyl)-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepine (I) with borane-THF complex catalyzed by (R)-2-amino-3-methyl-1,1-diphenyl-1-butanol (II) in dichloromethane gives the 8(R)-methyl derivative (III), which is acetylated with acetic anhydride yielding the 7-acetyl-8(R)-methyl derivative (IV). Finally, the nitro group of (IV) is reduced with hydrazine and Ni-Raney in methanol.

参考文献中间体

合成目标

【1】 Ling, I.; et al.; Asymmetric reduction of a carbon-nitrogen double bond: Enantioselective synthesis of 4,5-dihydro-3H-2,3-benzodiazepines. J Chem Soc - Perkins Trans I 1995, 11, 1423.
【2】 Ling, I.; Hamori, T.; Botka, P.; Solyom, S.; Simay, A.; Moravcsik, I. (Gyogyszerkutato Intezet Kft.); Optically active 1-(4-nitrophenyl)-4-methyl-7, 8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine and process for preparing same. WO 9501357 .
【3】 Andrasi, F.; Berzsenyi, P.; Botka, P.; Farkas, S.; Goldschmidt, K.; Hamori, T.; Korosi, J.; Moravcsik, I.; Tarnawa, I. (Gyogyszerkutato Intezet Kft.); N-Acyl-2,3-benzodiazepine derivs., pharmaceutical compsns. containing them and process for preparing same. EP 0492485; JP 1993070463; US 5519019; US 5521174; US 5536832; US 5604223; US 5639751 .
【4】 Berzsenyi, P.; Goldschmidt, K.; Moravcsik, I.; Kórösi, J.; Andrási, F.; Farkas, S.; Hámori, T.; Tarnawa, I.; Botka, P. (Gyogyszerkutato Intezet Kft.); N-Acyl-2,3-benzodiazepine derivs., pharmaceutical compsns. containing them and process for preparing same. US 5459137 .

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)	29266	8-methyl-5-(4-nitrophenyl)-9H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine		C₁₇H₁₃N₃O₄	详情	详情
(II)	10103	(2R)-2-Amino-3-methyl-1,1-diphenyl-1-butanol	56755-20-5 (hydrochloride)	C₁₇H₂₁NO	详情	详情
(III)	29267	(8R)-8-methyl-5-(4-nitrophenyl)-8,9-dihydro-7H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine		C₁₇H₁₅N₃O₄	详情	详情
(IV)	29265	1-[(8R)-8-methyl-5-(4-nitrophenyl)-8,9-dihydro-7H-[1,3]dioxolo[4,5-h][2,3]benzodiazepin-7-yl]-1-ethanone		C₁₉H₁₇N₃O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The cyclization of benzophenone (I) with hydrazine in isopropanol gives 8-methyl-5-(4-nitrophenyl)-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepine (II), which is treated with KCN in AcOH at 70 C in a sealed tube to afford nitrile (III). Subsequent treatment of (III) with acetyl chloride gave the N-acetyl benzodiazepine (IV). Finally, the nitro group of (IV) was reduced to the target amine by transfer hydrogenation using hydrazine and Pd/C.

参考文献中间体

合成目标

【1】 Andrási, F.; Balogh, T.; Botka, P.; Elekes, I.; Goldschmidt, K.; Hámori, T.; Korosi, J.; Láng, T.; Moravcsik, I.; Sineger, E.; Somogyi, G.; Zolyomi, G. (Egis Pharmaceuticals Ltd.); 5H-2,3-Benzodiazepine derivs., process for their preparation and pharmaceutical compsns. which contain them. FR 2566774; HU 191702 .
【2】 8-Substd.-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepine derivs., as AMPA/kainate receptor inhibitors. EP 1003749; WO 9907707 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	19273	acetyl chloride	75-36-5	C₂H₃ClO	详情	详情
(I)	35397	1-[6-(4-nitrobenzoyl)-1,3-benzodioxol-5-yl]acetone		C₁₇H₁₃NO₆	详情	详情
(II)	29266	8-methyl-5-(4-nitrophenyl)-9H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine		C₁₇H₁₃N₃O₄	详情	详情
(III)	35398	8-methyl-5-(4-nitrophenyl)-8,9-dihydro-7H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine-8-carbonitrile		C₁₈H₁₄N₄O₄	详情	详情
(IV)	35399	7-acetyl-8-methyl-5-(4-nitrophenyl)-8,9-dihydro-7H-[1,3]dioxolo[4,5-h][2,3]benzodiazepine-8-carbonitrile		C₂₀H₁₆N₄O₅	详情	详情

Extended Information