2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】24173

【品名】2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylic acid

【CA登记号】

【分子式】C₁₃H₁₇NO₄

【分子量】251.28232

【元素组成】C 62.14% H 6.82% N 5.57% O 25.47%

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：(II)

Synthesis of intermediate (VI): 2) The reaction of 5,8-dimethoxy-2-tetralone (I) with KCN and ammonium carbonate in refluxing ethanol gives 2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoic acid (II), which is acetilated with acetic anhydride to give 2-acetylamino-1,2,3,4-tetrahydro-2-naphthoic acid (XV), which is submitted to optical resolution with I-alpha-phenylethylamine yielding the 2(R) isomer (XVI). Esterification of (XVI) with methanol-H2SO4 affords the corresponding methyl ester (XVII), which by reaction first with NaH and DMSO and then with Al-Hg in THF is converted into the acetyl derivative (VI).

参考文献中间体

合成目标

【1】 Ishizumi, K.; Ohashi, N.; Tanno, N.; Sato, H.; Fukui, M.; Morisada, S. (Sumitomo Pharmaceuticals Co., Ltd.); Aminonaphthacene derivs.. EP 0107486; US 4673668 .
【2】 Hoshi, A.; Prous, J.; Castaner, J.; SM-5887. Drugs Fut 1988, 13, 11, 962.
【3】 Ishizumi, K.; et al.; Stereospecific total synthesis of 9-aminoanthracyclines: (+)-9-Amino-9-deoxydaunomycin and related compounds. J Org Chem 1987, 52, 20, 4477-85.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	24172	5,8-dimethoxy-3,4-dihydro-2(1H)-naphthalenone	C₁₂H₁₄O₃	详情	详情
(II)	24173	2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylic acid	C₁₃H₁₇NO₄	详情	详情
(VI)	24175	N-[(2R)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenyl]acetamide	C₁₆H₂₁NO₄	详情	详情
(XV)	24174	2-(acetamido)-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylic acid	C₁₅H₁₉NO₅	详情	详情
(XVI)	24177	(2R)-2-(acetamido)-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylic acid	C₁₅H₁₉NO₅	详情	详情
(XVII)	24176	methyl (2R)-2-(acetamido)-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylate	C₁₆H₂₁NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Synthesis of intermediate (VI): 1) The reaction of 5,8-dimethoxy-2-tetralone (I) with KCN and ammonium carbonate in refluxing ethanol gives 2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthoic acid (II), which is esterified with methanol-HCl to the corresponding methyl ester (III). The optical resolution of (III) with D-(-)-mandelic acid affords the 2R isomer (IV), which by reaction first with NaH and DMSO and then with Zn and NaOH in water gives (R)-2-acetyl-2-amino-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (V). The acetylation of (V) with acetic anhydride in pyridine yields (R)-2-acetyl-2-acetamido-5,8-dimethoxy-1,2,3,4-tetrahydronaphthalene (VI).

参考文献中间体

合成目标

【1】 Ishizumi, K.; Ohashi, N.; Tanno, N.; Sato, H.; Fukui, M.; Morisada, S. (Sumitomo Pharmaceuticals Co., Ltd.); Aminonaphthacene derivs.. EP 0107486; US 4673668 .
【2】 Ishizumi, K.; et al.; Stereospecific total synthesis of 9-aminoanthracyclines: (+)-9-Amino-9-deoxydaunomycin and related compounds. J Org Chem 1987, 52, 20, 4477-85.
【3】 Hoshi, A.; Prous, J.; Castaner, J.; SM-5887. Drugs Fut 1988, 13, 11, 962.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	24172	5,8-dimethoxy-3,4-dihydro-2(1H)-naphthalenone	C₁₂H₁₄O₃	详情	详情
(II)	24173	2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylic acid	C₁₃H₁₇NO₄	详情	详情
(III)	24180	methyl 2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylate	C₁₄H₁₉NO₄	详情	详情
(IV)	24181	methyl (2R)-2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenecarboxylate	C₁₄H₁₉NO₄	详情	详情
(V)	24182	1-[(2R)-2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenyl]-1-ethanone	C₁₄H₁₉NO₃	详情	详情
(VI)	24175	N-[(2R)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthalenyl]acetamide	C₁₆H₂₁NO₄	详情	详情

Extended Information