10-bromo-4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione -Drug Synthesis Database

【结构式】

【分子编号】60173

【品名】10-bromo-4,5,6,7-tetrahydro-1H-cyclopenta[a]pyrrolo[3,4-c]carbazole-1,3(2H)-dione

【CA登记号】

【分子式】C₁₇H₁₁BrN₂O₂

【分子量】355.19062

【元素组成】C 57.49% H 3.12% Br 22.5% N 7.89% O 9.01%

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：(VI)

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

参考文献中间体

合成目标

【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：(IX)

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.

参考文献中间体

合成目标

【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