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【结 构 式】

【分子编号】60172

【品名】4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione

【CA登记号】

【 分 子 式 】C17H12N2O2

【 分 子 量 】276.29456

【元素组成】C 73.9% H 4.38% N 10.14% O 11.58%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IV)

The selective methylation of 5,6,7,8-tetrahydro-5,8-ethanonaphthalene-1,4-diol (I) with dimethylsulfate in a two phase system gives 4-methoxy-5,6,7,8-tetrahydro-5,8-ethano-1-naphthol (II), which is condensed with epichlorohydrin (III) by means of piperidine at 100 C yielding 1-methoxy-4-(2,3-epoxypropoxy)-5,6,7,8-tetrahydro-5,8-ethanonaphthalene (IV). The reaction of (IV) with tert-butylamine (V) at 100 C affords 1-methoxy-4-[3-(tert-butylamino)-2-hydroxypropoxy]-5,6,7,8-tetrahydro-5,8-ethanonaphthalene (VI), which is finally demethylated by treatment with pyridine hydrochloride at 160 C

1 Blancafort, P.; Serradell, M.N.; Castaner, J.; McGillion, F.B.; Nafetolol. Drugs Fut 1981, 6, 2, 92.
2 Momiyama, N.; Ichikawa, Y.; Hasegawa, S.; Ishikawa, T.; Matsuyama, R.; Miazaki, K.; Shimada, H.; Targeting MMP-7 via antisense oligonucleotide shows anti-metastatic effects in a colon cancer murine model. Eur J Med Chem 1974, 9, 5, 501.
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) 61070 tricyclo[6.2.2.0~2,7~]dodeca-2,4,6-triene-3,6-diol C12H14O2 详情 详情
(II) 61071 6-methoxytricyclo[6.2.2.0~2,7~]dodeca-2,4,6-trien-3-ol C13H16O2 详情 详情
(III) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(IV) 60172 4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione C17H12N2O2 详情 详情
(V) 17895 2-Amino-2-methylpropane; tert-butylamine; 2-methyl-2-propanamine 75-64-9 C4H11N 详情 详情
(VI) 60173 10-bromo-4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione C17H11BrN2O2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VIII)

Indole (I) is protected as the indole N-carboxylate (II) by treatment of its lithio derivative with carbon dioxide gas in cold THF. Subsequent metalation with tert-butyllithium, followed by addition to cyclopentanone (III) gives rise to the carbinol adduct (IV). Dehydration of (IV) under acidic conditions furnishes 2-(1-cyclopentenyl)indole (V). Diels-Alder condensation of (V) with maleimide (VI) at 190 C provides the pentacyclic system (VII). Further dehydrogenation of (VII) employing DDQ leads to the fused carbazole compound (VIII). Regioselective halogenation of (VIII) at position 3 by means of NBS yields the corresponding aryl bromide (IX). Then, displacement of the bromide group of (IX) with either CuCN or Zn(CN)2 produces nitrile (X). This is finally reduced to the primary amine by catalytic hydrogenation in the presence of Raney nickel and ammonia.

1 Chatterjee, S.; Ator, M.A.; Hudkins, R.L.; Bihovsky, R.; Dunn, D. (Cephalon, Inc.); Novel multicyclic cpds. and the use thereof. WO 0185686 .
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) 15292 Indole; 1H-indole 120-72-9 C8H7N 详情 详情
(II) 60168 1H-indole-1-carboxylate C9H6NO2 详情 详情
(III) 15113 cyclopentanone 120-92-3 C5H8O 详情 详情
(IV) 60169 1-(1H-indol-2-yl)cyclopentanol C13H15NO 详情 详情
(V) 60170 2-(1-cyclopenten-1-yl)-1H-indole C13H13N 详情 详情
(VI) 19711 1H-pyrrole-2,5-dione 541-59-3 C4H3NO2 详情 详情
(VII) 60171 3a,3b,4,5,6,6a,7,11c-octahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione C17H16N2O2 详情 详情
(VIII) 60172 4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione C17H12N2O2 详情 详情
(IX) 60173 10-bromo-4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione C17H11BrN2O2 详情 详情
(X) 60174 1,3-dioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-10-carbonitrile C18H11N3O2 详情 详情
Extended Information