1,2-Dihydro-4-(6-iodohexyloxy)-1,2-dioxonaphthalene → 2'-[4-[6-(1,2-Dihydro-1,2-dioxo-naphth-4-yl)oxyhexyl]oxyphenyl]-5-(4-methylpiperazin-1-yl)-2,5'-bi-1h-benzimidazole

HRID 393876Notes

Reaction equation

HRID 393876 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]3[N:14]=[C:15]([C:17]4[CH:22]=[CH:21][C:20]5[NH:23][C:24]([NH:32][C:19]=5[CH:18]=4)=[C:25]4[CH:31]=[CH:30][C:28](=[O:29])[CH:27]=[CH:26]4)[NH:16][C:10]=3[CH:9]=2)[CH2:4][CH2:3]1.I[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][O:40][C:41]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:44](=[O:51])[C:43](=[O:52])[CH:42]=1>CO.CN(C=O)C.O>[O:51]=[C:44]1[C:45]2[C:50](=[CH:49][CH:48]=[CH:47][CH:46]=2)[C:41]([O:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][O:29][C:28]2[CH:30]=[CH:31][C:25]([C:24]3[NH:23][C:20]4[CH:21]=[CH:22][C:17]([C:15]5[NH:14][C:11]6[CH:12]=[CH:13][C:8]([N:5]7[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]7)=[CH:9][C:10]=6[N:16]=5)=[CH:18][C:19]=4[N:32]=3)=[CH:26][CH:27]=2)=[CH:42][C:43]1=[O:52]

Participants

6

Reactant 2

HCID 226477941,2-Dihydro-4-(6-iodohexyloxy)-1,2-dioxonaphthaleneHCID 178480630HCID 178480630, compound

Product 1

HCID 1784806372'-[4-[6-(1,2-Dihydro-1,2-dioxo-naphth-4-yl)oxyhexyl]oxyphenyl]-5-(4-methylpiperazin-1-yl)-2,5'-bi-1h-benzimidazoleYield 30.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Hoechst 33258 (3.0 g, 5 mmol) was dissolved in a hot mixture of isopropanol-water (24 mL/12 mL) and neutralized with ammonium hydroxide (3 mL). The precipitate was filtered, triturated with Et2O and dried in vacuo to obtain the free base of bisbenzimidazole. A 1.0 M solution of Bu4NOH in MeOH (0.6 mL, 0.6 mmol) was added to the solution of bisbenzimidazole (1.635 g, 3.85 mmol) in MeOH (30 mL), stirred for 15 min and concentrated to dryness in vacuo. Iodonaphthoquinone 5 (1.485 g, 3.87 mmol) in DMF (30 mL) was added to the tetrabutyl ammonium salt and the mixture was stirred for 48 h. The reaction mixture was suspended in H2O, the crude product was filtered, washed with H2O, dried and purified by flash chromatography (MeOH/CHCl3 1:9, 1:5) to afford 14 as a yellow solid (790 mg, 30%). 1H NMR (CDCl3/MeOH-d4) 8.21 (s, 1H), 8.09 (d, J=7.6 Hz, 1H), 8.05 (d, J=8.7 Hz, 2H), 7.85-7.95 (m, 2H), 7.48-7.75 (m, 4H), 7.14 (bs, 1H), 7.10-6.98 (m 3H), 4.21 (t, J=6.3 Hz, 2H), 4.08 (t, J=6.2 Hz, 2H), 2.65-2.75 (m, 4H), 2.40 (s, 3H), 1.80-2.15 (m, 4H), 1.60-1.75 (m, 4H). MS (LSIMS, 3-NBA) 725.2 (M++1).

Workup

  1. concentrationconcentrated to dryness in vacuo
  2. stirringthe mixture was stirred for 48 h
  3. filtrationthe crude product was filtered
  4. washwashed with H2O
  5. customdried
  6. custompurified by flash chromatography (MeOH/CHCl3 1:9, 1:5)

Sources & evidence

ORD record
ord-40a0f4dc20444355ba7e027f0ce013c3
Source dataset
uspto-grants-2004_10
Patent number
US06809176B2

Reaction notes

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