5-bromo-6-nitroindane -Drug Synthesis Database

【结构式】

【分子编号】21478

【品名】5-bromo-6-nitroindane

【CA登记号】

【分子式】C₉H₈BrNO₂

【分子量】242.07206

【元素组成】C 44.66% H 3.33% Br 33.01% N 5.79% O 13.22%

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 acetylation of 5-aminoindane (I) with acetic anhydride gives N-(5-indanyl)acetamide (II), which is nitrated with HNO3 in glacial acetic acid yielding N-(6-nitro-5-indanyl)acetamide (III) and a small amount of the isomer (IV). The product (III) is hydrolyzed with HCl to 6-nitro-5-indanylamine (V). This nitroamine can also be obtained by nitration of 5-aminoindane (I). The Sandmeyer reaction of 6-nitro-5-indanylamine (V) with HNO2 and CuBr/NaBr in HBr leads to 6-nitro-5-bromoindane (VI), which reacts with 2,4-difluorophenol in the presence of KOC(CH3)3/CuCl in tert-butanol to yield 6-nitro-5-(2,4-difluorophenoxy)indane (VII). Starting from (VII), CGP-28238 can be prepared by two different routes: a) Condensation of (VII) with tert-butoxy-bis(dimethylamino)methane followed by ozonolysis of the enamine (VIII), and reduction of the nitro group using Raney-Ni and hydrazine hydrate yields 5-amino-6-(2,4-difluorophenoxy)-1-indanone (X). In the last step the intermediate (X) is mesylated with mesylchloride to give CGP-28238. b) Reduction of (VII) using Raney-Ni and hydrazine hydrate gives 5-amino-6-(2,4-difluorophenoxy)indane (XI), which is acetylated with acetic anhydride and oxidized with CrO3 to yield a mixture of indanone (XII) and (XIII). Chromatographic separation and hydrolysis of (XII) with HCl in ethanol gives 5-amino-6-(2,4-difluorophenoxy)-1-indanone (X), which can be mesylated, as before, to CGP-28238.

参考文献中间体

合成目标

【1】 Schroder, E.; Rufer, C.; Bottcher, I.; Kapp, J.-F. (Schering AG); Novel indanyl derivs., their preparation and use. EP 0056956; US 4375479 .
【2】 Rufer, C.; Bahlmann, F.; Schroder, E.; Bottcher, I.; Non-steroidal antiinflammatory compounds. 8. Antii. Eur J Med Chem 1982, 17, 1, 173-80.
【3】 Schroder, E.; Lehmann, M.; Rufer, C.; Bottcher, I.; Non-steroidal antiinflammatory compounds. 6. Antii. Eur J Med Chem 1982, 17, 1, 35-42.
【4】 Wiesenberg, I.; Ferrini, P.G.; CGP-28238. Drugs Fut 1989, 14, 11, 1035.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	21486	2,4-difluorophenol	367-27-1	C₆H₄F₂O	详情	详情
(B)	21487	N-[tert-butoxy(dimethylamino)methyl]-N,N-dimethylamine		C₉H₂₂N₂O	详情	详情
(I)	21473	5-indanamine; 2,3-dihydro-1H-inden-5-ylamine	24425-40-9	C₉H₁₁N	详情	详情
(II)	21474	N-(2,3-dihydro-1H-inden-5-yl)acetamide		C₁₁H₁₃NO	详情	详情
(III)	21475	N-(6-nitro-2,3-dihydro-1H-inden-5-yl)acetamide		C₁₁H₁₂N₂O₃	详情	详情
(IV)	21476	N-(4-nitro-2,3-dihydro-1H-inden-5-yl)acetamide		C₁₁H₁₂N₂O₃	详情	详情
(V)	21477	6-nitro-2,3-dihydro-1H-inden-5-ylamine; 6-nitro-5-indanamine		C₉H₁₀N₂O₂	详情	详情
(VI)	21478	5-bromo-6-nitroindane		C₉H₈BrNO₂	详情	详情
(VII)	21479	5-(2,4-difluorophenoxy)-6-nitroindane		C₁₅H₁₁F₂NO₃	详情	详情
(VIII)	21480	N-[[6-(2,4-difluorophenoxy)-5-nitro-2,3-dihydro-1H-inden-1-ylidene]methyl]-N,N-dimethylamine		C₁₈H₁₆F₂N₂O₃	详情	详情
(IX)	21481	6-(2,4-difluorophenoxy)-5-nitro-1-indanone		C₁₅H₉F₂NO₄	详情	详情
(X)	21482	5-amino-6-(2,4-difluorophenoxy)-1-indanone		C₁₅H₁₁F₂NO₂	详情	详情
(XI)	21483	6-(2,4-difluorophenoxy)-2,3-dihydro-1H-inden-5-ylamine		C₁₅H₁₃F₂NO	详情	详情
(XII)	21484	N-[6-(2,4-difluorophenoxy)-1-oxo-2,3-dihydro-1H-inden-5-yl]acetamide		C₁₇H₁₃F₂NO₃	详情	详情
(XIII)	21485	N-[6-(2,4-difluorophenoxy)-3-oxo-2,3-dihydro-1H-inden-5-yl]acetamide		C₁₇H₁₃F₂NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

A) Synthesis of intermediate (VII): The acetylation of 5-aminoindane (I) with acetic anhydride gives N-(5-indanyl)acetamide (II), which is nitrated with HNO3 in glacial acetic acid yielding N-(6-nitro-5-indanyl)acetamide (III) and a small amount of the isomer (IV). The product (III) is hydrolyzed with HCl to 6-nitro-5-indanylamine (V). This nitroamine can also be obtained by nitration of 5-aminoindane (I). The Sandmeyer reaction of 6-nitro-5-indanylamine (V) with HNO2 and CuBr/NaBr in HBr gives 6-nitro-5-bromoindane (VI), which reacts with phenol in the presence of either K2CO3/ CuCl in pyridine (Method A) or t-BuOK in DMF (Method B) or t-BuOK/CuCl in tert-butanol (Method C) to yield 6-nitro-5-phenoxyindane (VII).

参考文献中间体

合成目标

【1】 Ferrini, P.G.; Bottcher, I.; CGP-28237. Drugs Fut 1987, 12, 1, 9.
【2】 Schroder, E.; Lehmann, M.; Rufer, C.; Bottcher, I.; Non-steroidal antiinflammatory compounds. 6. Antii. Eur J Med Chem 1982, 17, 1, 35-42.
【3】 Rufer, C.; Bahlmann, F.; Schroder, E.; Bottcher, I.; Non-steroidal antiinflammatory compounds. 8. Antii. Eur J Med Chem 1982, 17, 1, 173-80.

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)	21473	5-indanamine; 2,3-dihydro-1H-inden-5-ylamine	24425-40-9	C₉H₁₁N	详情	详情
(II)	21474	N-(2,3-dihydro-1H-inden-5-yl)acetamide		C₁₁H₁₃NO	详情	详情
(III)	21475	N-(6-nitro-2,3-dihydro-1H-inden-5-yl)acetamide		C₁₁H₁₂N₂O₃	详情	详情
(IV)	21476	N-(4-nitro-2,3-dihydro-1H-inden-5-yl)acetamide		C₁₁H₁₂N₂O₃	详情	详情
(V)	21477	6-nitro-2,3-dihydro-1H-inden-5-ylamine; 6-nitro-5-indanamine		C₉H₁₀N₂O₂	详情	详情
(VI)	21478	5-bromo-6-nitroindane		C₉H₈BrNO₂	详情	详情
(VII)	23070	6-nitro-2,3-dihydro-1H-inden-5-yl phenyl ether; 5-nitro-6-phenoxyindane		C₁₅H₁₃NO₃	详情	详情

Extended Information