3,4-dibromo-1-methyl-1H-pyrrole-2,5-dione -Drug Synthesis Database

【结构式】

【分子编号】31468

【品名】3,4-dibromo-1-methyl-1H-pyrrole-2,5-dione

【CA登记号】

【分子式】C₅H₃Br₂NO₂

【分子量】268.89236

【元素组成】C 22.33% H 1.12% Br 59.43% N 5.21% O 11.9%

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：(I)

The Grignard condensation of pyrrolinedione (I) with 7-chloroindol-1-ylmagnesium bromide (II) in toluene gives the monoaddition product (III), which is condensed with indol-1-ylmagnesium bromide (IV) to yield the disubstituted compound (V). The hydrogenation of (V) with H2 over Pd/C in DMF affords the tetrahydro derivative (VI), which is condensed with the aminosugar (VII) in DMF and dehydrogenated with DDQ or DBU to afford the adduct (VIII). Finally, the methylamino group of (VIII) is deprotected by means of TBAF in THF.

参考文献中间体

合成目标

【1】 Van Vranken, D.L.; Chisholm, J.D.; Regiocontrolled synthesis of the antitumor antibiotic AT2433-A1. J Org Chem 2000, 65, 22, 7541.

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)	31468	3,4-dibromo-1-methyl-1H-pyrrole-2,5-dione		C₅H₃Br₂NO₂	详情	详情
(II)	45582	bromo(7-chloro-1H-indol-1-yl)magnesium		C₈H₅BrClMgN	详情	详情
(III)	45583	3-bromo-4-(7-chloro-1H-inden-3-yl)-1-methyl-1H-pyrrole-2,5-dione		C₁₄H₉BrClNO₂	详情	详情
(IV)	45584	bromo(1H-indol-1-yl)magnesium		C₈H₆BrMgN	详情	详情
(V)	45585	3-(7-chloro-1H-indol-3-yl)-4-(1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione		C₂₁H₁₄ClN₃O₂	详情	详情
(VI)	45586	(4bR,4cR,7aR,12bS)-1-chloro-6-methyl-7a,12,12b,13-tetrahydro-4bH-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(4cH,6H)-dione	577-59-3	C₂₁H₁₆ClN₃O₂	详情	详情
(VII)	45587	2-(trimethylsilyl)ethyl (3S,4S,6S)-4-hydroxy-6-[[(2R,3S,4R,5R,6R)-4,5,6-trihydroxy-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-yl(methyl)carbamate		C₁₉H₃₇NO₁₀Si	详情	详情
(VIII)	45588	2-(trimethylsilyl)ethyl (3S,4S,6S)-6-[[(2R,3S,4R,5R,6R)-6-(11-chloro-6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-4,5-dihydroxy-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]-4-hydroxytetrahydro-2H-pyran-3-yl(methyl)carbamate		C₄₀H₄₇ClN₄O₁₁Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of 6-(benzyloxy)indolylmagnesium bromide (I) with dihalomaleimide (II) afforded the diindolylmaleimide (III), which was oxidatively cyclized to produce indolocarbazole (IV). Glycosylation of (IV) with 1-chloro-tetrabenzylglucose (V) yielded the glycosyl derivative (VI). Subsequent deprotection of the benzyl ethers of (VI) by hydrogenolysis over Pd/C gave (VII). Conversion of the imide function of (VII) to anhydride (VIII) was then effected by treatment with KOH. Finally, coupling of (VIII) with hydrazine (IX) in DMF at 80 C yielded the title compound.

参考文献中间体

合成目标

【1】 Ohkubo, M.; Nishimura, I.; Honma, T.; Nishimura, T.; Suda, H.; Morishima, H.; Arakawa, H.; Yoshinari, T.; Ito, S.; Nishimura, S.; Synthesis and biological activities of NB-506 analogues: Effects of the positions of two hydroxyl groups at the indole rings. Bioorg Med Chem Lett 1999, 9, 23, 3307.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	31467	[6-(benzyloxy)-1H-indol-1-yl](bromo)magnesium	C₁₅H₁₂BrMgNO	详情	详情
(II)	31468	3,4-dibromo-1-methyl-1H-pyrrole-2,5-dione	C₅H₃Br₂NO₂	详情	详情
(III)	31469	3,4-bis[6-(benzyloxy)-1H-indol-3-yl]-1-methyl-1H-pyrrole-2,5-dione	C₃₅H₂₇N₃O₄	详情	详情
(IV)	31470	2,10-bis(benzyloxy)-6-methyl-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	C₃₅H₂₅N₃O₄	详情	详情
(V)	31471	(2R,3S,4S,5R,6S)-3,4,5-tris(benzyloxy)-2-[(benzyloxy)methyl]-6-chlorotetrahydro-2H-pyran; benzyl (2R,3S,4S,5R,6S)-3,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-chlorotetrahydro-2H-pyran-4-yl ether	C₃₄H₃₅ClO₅	详情	详情
(VI)	31472	2,10-bis(benzyloxy)-6-methyl-12-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	C₆₉H₅₉N₃O₉	详情	详情
(VII)	31473	2,10-dihydroxy-6-methyl-12-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione	C₂₇H₂₃N₃O₉	详情	详情
(VIII)	31474	2,10-dihydroxy-12-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]-12,13-dihydrofuro[3,4-c]indolo[2,3-a]carbazole-5,7-dione	C₂₆H₂₀N₂O₁₀	详情	详情
(IX)	31434	2-hydrazino-1,3-propanediol	C₃H₁₀N₂O₂	详情	详情

Extended Information