M. Hebenbrock and J. Müller: Two new intercalating agents for DNAꢂꢁꢀꢀꢀꢂ7
(
161mg,0.530mmol,0.2equiv.)andK CO (2.95g,21.4mmol, Et O as antisolvent. The crystalline solid was dissolved
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3
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.0 equiv.) were degassed in a solution of dimethoxyethane in acetone (10 mL) and stirred for 6 h at 60°C. Following
(
17 mL) and water (17 mL). Following the addition of the addition of KPF (644 mg, 3.50 mmol, 3.5 equiv.), the
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Pd(OAc) (35 mg, 0.13 mmol, 0.05 equiv.), the solution was solvent was removed in vacuo, and the solid residue was
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stirred for 1 d at 110°C. After extracting with CH Cl , the com- washed with water, ethanol and Et O. Compound (1a)PF
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bined organic layers were dried (MgSO ) and the solvent was isolated as a yellowish solid (391 mg, 0.790 mmol,
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removed in vacuo. The solid residue was filtered through 79%). – H NMR (400 MHz, [D ]DMSO, 27°C): δꢀ=ꢀ9.31–9.20
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Celite using Et O and the solvent removed in vacuo. The (m, 1H, H3), 9.19–9.08 (m, 1H, H6), 8.68–8.54 (m, 1H, H4),
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crude product was combined with compound 3a (404 mg, 8.41–8.15 (m, 5H, H17, H18, H19, H21), 8.13–8.01 (m, 2H,
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.05 mmol, 0.8 equiv.), [1,1′-bis(diphenylphosphino)fer- H11), 7.92–7.76 (m, 4H, H5, H12, H13), 7.72–7.53 (m, 3H, H22,
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rocene]dichloridopalladium(II) (75 mg, 0.10 mmol, 0.04 H23) ppm. – C NMR (101 MHz, [D ]DMSO, 27°C): δꢀ=ꢀ156.0
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equiv.) and Cs CO (868 mg, 2.46 mmol, 0.9 equiv.) and (C16), 149.6 (C14), 146.5 (C9), 142.1 (C2), 141.8 (C18), 141.1
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the mixture dried in vacuo for 5 h. Following the addi- (C4), 136.9 (C20), 132.7 (C13), 130.1 (C23), 129.7 (C11), 129.6
tion of toluene (10 mL), the solution was stirred for 18 h at (C12), 129.2 (C22), 128.0 (C6), 126.9 (C21), 121.9 (C10), 120.9
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00°C. The mixture was extracted with ethyl acetate, the (C17), 120.3 (C5), 114.0 (C3), 113.4 (C19) ppm. – N NMR
combined organic layers dried (MgSO ) and the solvent (41 MHz, [D ]DMSO, 27°C): δꢀ=ꢀ274 (N15), 201 (N7), 200 (N1)
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removed in vacuo. The crude product was purified by ppm. – HRMS ((ꢀ+)-ESI): m/zꢀ=ꢀ349.1462 (calcd. 349.1448 for
column chromatography (SiO , ethyl acetate-cyclohexane, [C H N ] ).
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+
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23 17
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0:1) to give compound 4a as a yellowish solid (610 mg,
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.73 mmol, 65%). According to the H NMR data, a mixture
of E and Z isomers was obtained (E:Zꢀ=ꢀ3.8:1.0). The assign- 4.5 Synthesis of 2-(2-benzylidenehydrazi-
ment of the E and Z isomer was made in comparison with
nyl)quinoline (3b)
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literature precedents [21, 22]. – H NMR (400 MHz, CDCl ,
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7°C, E isomer): δꢀ=ꢀ8.52–8.44 (m, 1H, H6), 7.91–7.80 (m, Compound 3b was synthesized in analogy to compound
H, H4, H18, H21), 7.72–7.49 (m, 6H, H3, H9, H11, H17, H19), 3a, starting from compound 2b (463 mg, 2.91 mmol).
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.42–7.28 (m, 6H, H12, H13, H22, H23), 7.17–7.09 (m, 1H, H5) The product was isolated as a brownish solid (591 mg,
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ppm. H NMR (400 MHz, CDCl , 27°C, Z isomer): δꢀ=ꢀ8.60– 2.39 mmol, 82%). – H NMR (400 MHz, CDCl , 27°C):
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.54 (m, 1H, H6), 7.91–7.80 (m, 3H, H9, H21), 7.74–7.43 (m, δꢀ=ꢀ10.35–9.00 (br, 1H, H11), 8.26–7.93 (m, 1H, H4), 7.93–7.49
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H, H3, H11, H17, H18, H19), 7.42–7.28 (m, 7H, H4, H12, H13, (m, 7H, H3, H6, H8, H9, H13, H15), 7.45–7.18 (m, 4H, H7, H16,
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H22, H23), 7.17–7.09 (m, 1H, H5) ppm. – C NMR (101 MHz, H17). – HRMS ((ꢀ+)-ESI): m/zꢀ=ꢀ248.1179 (calcd. 248.1188 for
+
CDCl , 27°C, E isomer): δꢀ=ꢀ156.2 (C14), 155.4 (C2), 155.1 (C16), [C H N ] ). – Analysis for C H N (%): calcd. C 77.7, H 5.3,
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16 14
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16 13
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48.8 (C6), 139.0 (C18), 138.8 (C20), 138.7 (C9), 138.1 (C4), N 17.0; found C 77.3, H 5.2, N 16.8.
35.6 (C10), 128.9 (C23), 128.8 (C13), 128.5 (C12), 128.5 (C22),
26.7 (C11), 126.7 (C21), 119.8 (C5), 118.1 (C3), 116.1 (C17), 115.5
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(
C19) ppm. N NMR (41 MHz, CDCl , 27°C, E isomer): δꢀ=ꢀ326 4.6 Synthesis of 2-(2-benzylidene-1-
3
(
N8), 292 (N1), 285 (N15), 162 (N7) ppm. – HRMS ((ꢀ+)-ESI):
(
6-phenylpyridin-2-yl)hydrazinyl)
+
m/zꢀ=ꢀ351.1614 (calcd. 351.1610 for [C H N ] ). – Analysis
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4
quinoline (4b)
for C H N ꢀꢀ·ꢀꢀ0.15 EtOAcꢀꢀ·ꢀꢀ2.75 H O (%): calcd. C 68.8, H 6.0,
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N 13.6; found C 68.7, H 5.6, N 13.4.
Compound 4b was synthesized in analogy to com-
pound 4a, using compound 3b (507 mg, 2.05 mmol).
The product was isolated as a yellowish solid (682 mg,
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.4 Synthesis of 3-phenyl-1-(6-phenylpyri-
1.70 mmol, 64%). – H NMR (400 MHz, CDCl , 27°C, E
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isomer): δꢀ=ꢀ8.25–8.19 (m, 1H, H4), 7.98–7.77 (m, 6H, H6,
din-2-yl)-1H-[1,2,4]triazolo[4,3-a]pyri-
H13, H15, H25), 7.73–7.56 (m, 10H, H3, H4, H8, H9, H11,
din-4-ium hexafluorophosphate ((1a)PF )
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H16, H17, H26), 7.55–7.41 (m, 2H, H7, H27), 7.40–7.29 (m,
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A solution of bromine (333 μL, 6.50 mmol, 6.5 equiv.) in 3H, H21, H22, H23) ppm. H NMR (400 MHz, CDCl , 27°C,
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acetic acid (4 mL) was added dropwise at 30°C within 1 h Z isomer): δꢀ=ꢀ8.30–8.25 (m, 1H, H4), 7.98–7.77 (m, 6H, H6,
to a solution of compound 4a (350 mg, 1.00 mmol) in acetic H13, H15, H25), 7.73–7.56 (m, 10H, H3, H4, H8, H9, H11,
acid (14 mL). Water (10 mL) was added, and the result- H16, H17, H26), 7.55–7.41 (m, 2H, H7, H27), 7.40–7.29 (m,
ing precipitate was washed with water and acetonitrile. 3H, H21, H22, H23) ppm. – HRMS ((ꢀ+)-ESI): m/zꢀ=ꢀ401.1761
+
The solid was recrystallized from DMF overnight using (calcd. 401.1766 for [C H N ] ).
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