methyl 4-(5,7,7,10,10-pentamethyl-7,8,9,10-tetrahydro-5H-naphtho[2,3-b][1,5]benzodiazepin-12-yl)benzoate -Drug Synthesis Database

【结构式】

【分子编号】43781

【品名】methyl 4-(5,7,7,10,10-pentamethyl-7,8,9,10-tetrahydro-5H-naphtho[2,3-b][1,5]benzodiazepin-12-yl)benzoate

【CA登记号】

【分子式】C₃₀H₃₂N₂O₂

【分子量】452.59636

【元素组成】C 79.61% H 7.13% N 6.19% O 7.07%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VIII)

Treatment of o-nitroaniline (I) with 6-bromo-1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphtalene (II), K2CO3 and CuI in xylene yields diphenylamine derivative (III), which is then N-methylated by means of NaH and MeI in DMF to provide (IV). Reduction of the nitro group of (IV) by hydrogenation over Pd/C in ethanol or by treatment with Fe and HCl in H2O/EtOH affords the corresponding amine derivative (V), which is then condensed with terephthalic acid monomethyl ester chloride (VI) in benzene/pyridine to furnish compound (VII). Cyclization of (VII) by means of polyphosphoric acid (PPA) in CH2Cl2 gives diazepin derivative (VIII), which is finally converted in the target product by first nitration with KNO3 in H2SO4 followed by hydrolysis with NaOH in EtOH.

参考文献中间体

合成目标

【1】 Ohta, K.; Ebisawa, M.; Umemiya, H.; et al.; Retinoid X receptor-antagonistic diazepinylbenzoic acids. Chem Pharm Bull 1999, 47, 12, 1778.
【2】 Shudo, K. (Nikken Chemicals Co., Ltd.); Cpds. potentiating retinoid. JP 1998059951; US 5929069; US 6121256; WO 9711061 .

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)	11608	o-Nitroaniline; 2-Nitroaniline; 2-Nitrophenylamine	88-74-4	C₆H₆N₂O₂	详情	详情
(II)	43776	6-bromo-1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphthalene		C₁₄H₁₉Br	详情	详情
(III)	43777	5,5,8,8-tetramethyl-N-(2-nitrophenyl)-5,6,7,8-tetrahydro-2-naphthalenamine; N-(2-nitrophenyl)-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)amine		C₂₀H₂₄N₂O₂	详情	详情
(IV)	43778	N-methyl-N-(2-nitrophenyl)-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)amine; N,5,5,8,8-pentamethyl-N-(2-nitrophenyl)-5,6,7,8-tetrahydro-2-naphthalenamine		C₂₁H₂₆N₂O₂	详情	详情
(V)	43779	N-(2-aminophenyl)-N-methyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)amine; N(1)-methyl-N(1)-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1,2-benzenediamine		C₂₁H₂₈N₂	详情	详情
(VI)	25029	p-Phthalic acid monomethyl ester chloride; Terephthalic acid monomethyl ester chloride; Methyl 4-chlorocarbonylbenzoate	7377-26-6	C₉H₇ClO₃	详情	详情
(VII)	43780	methyl 4-([2-[methyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)amino]anilino]carbonyl)benzoate		C₃₀H₃₄N₂O₃	详情	详情
(VIII)	43781	methyl 4-(5,7,7,10,10-pentamethyl-7,8,9,10-tetrahydro-5H-naphtho[2,3-b][1,5]benzodiazepin-12-yl)benzoate		C₃₀H₃₂N₂O₂	详情	详情

Extended Information