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R. Csuk et al. · An Unprecedented Flupirtine Dimer
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(3.48). – H NMR (400 MHz, [D6]DMSO): δ = 7.41−7.33 After dilution with the double volume of hexane, the pre-
(m, 3 H, 4-H, 2 × 9-H), 7.12−7.06 (m, 2 H, 2 × 10-H), 4.48 cipitated product was collected by filtration and washed
(d, J = 6.1 Hz, 2 H, 7-CH2), 4.05 (q, J = 7.1 Hz, 2 H, 13- with a mixture of hexane-THF-diethyl ether (2 : 1 : 1) and
CH2), 1.21 (t, J = 6.9 Hz, 3 H, 14-CH3) ppm. – 13C NMR finally dried overnight. Re-precipitation from THF with
(100 MHz, [D6]DMSO): δ = 161.0 (d, 1JC,F = 241.6 Hz, C- hexane gave 4 (5.46 g, 69.0%) as a slightly off-white
11), 155.0 (C-12, C =O), 152.1 (C-2), 150.7 (C-6), 137.2 (d, solid. – HPLC/DAD (LaChrom D-7000, Merck-Hitachi):
4JC,F = 2.9 Hz, C-8), 137.2 (C-4), 129.3 (d, JC,F = 8.0 Hz, Nucleosil 100 – 5 C18−AB (Macherey-Nagel), 35 ◦C, 30%
3
C-9), 114.7 (d, JC,F = 21.1 Hz, C-10), 107.9 (C-3), 87.2 CH3CN/phosphate buffer (50 mM, pH = 2.8), 1 mL min−1
,
2
(C-5), 60.2 (C-13, CH2), 43.4 (C-7), 14.6 (C-14, CH3) retention time 12.5 min (retention time 1: 4.5 min); m. p.
ppm. – 19F NMR (376 MHz, [D6]DMSO): δ = −116.8 (tt, 244 ◦C. – Rf = 0.58 (hexane-THF, 1 : 1). – IR (KBr):
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3JF,H = 8.9 Hz, JF,H = 5.7 Hz) ppm. – MS ((–)-ESI): m/z ν = 3392m, 3324s, 2983w, 2850w, 1682s, 1638m, 1586m,
(%) = 380.9 (83) [M−H]−, 383.0 (100) [M−H]−, 335.2 (19) 1528s, 1430s, 1384m, 1221s, 1157w, 1060m, 824w, 770w,
[M−EtOH]−, 337.2 (19) [M−EtOH]−. – C15H16BrFN4O2 602w, 577w, 501w cm−1. – UV/Vis (MeOH): λmax (log
(383.22): calcd. C 47.02, H 4.21, N, 14.62; found C 46.85, H ε) = 206 (3.83), 251 (3.41), 328 nm (3.37). – 1H NMR
4.41, N 14.60.
(500 MHz, [D6]DMSO): δ = 7.34−7.30 (m, 4 H, 4 × 9-H),
7.04−6.99 (m, 4 H, 4 × 10-H), 6.99−6.95 (brs, 2 H, 2 × 4-
H), 4.47−4.36 (m, 4 H, 2 × 7-CH2), 4.05 (brq, J = 7.0 Hz,
4 H, 2 × 13-CH2), 1.21 (brt, J = 6.2 Hz, 6 H, 2 × 14-CH3)
ppm. – 13C NMR (125 MHz, [D6]DMSO): δ = 161.0 (d,
1JC,F = 241.5 Hz, C-11), 155.0 (C-12, C =O), 152.1 (C-6),
Diethyl 6-bromo-5-[(4-fluorobenzyl)amino]-2-oxo-
1H-imidazo[4,5-b]pyridine-1,3(2H)-dicarboxylate (11)
Compound 11 (1.42 g, 10%) was obtained as a colorless
solid; m. p. 162 ◦C. – Rf = 0.63 (chloroform-ethyl acetate,
9 : 1). – IR (KBr): ν = 3409s, 2984w, 2938w, 1802s, 1726s,
1622s, 1510s, 1427s, 1372s, 1334s, 1221s, 1148s, 1072m,
1038m, 898w, 856m, 767m, 745m, 692m, 613w, 546w, 476w
cm−1. – UV/Vis (MeOH): λmax(logε) = 258 (3.53), 337 nm
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151.9 (C-2), 137.5 (d, JC,F = 2.8 Hz, C-8), 136.6 (C-4),
129.4 (d, 3JC,F = 7.9 Hz, C-9), 114.6 (d, 2JC,F = 21.0 Hz, C-
10), 107.5 (C-3), 104.8 (C-5), 60.1 (C-13, CH2), 43.7 (C-7),
14.6 (C-14, CH3) ppm. – 19F NMR (376 MHz, [D6]DMSO):
δ = −117.0 (tt, 3JF,H = 9.1 Hz, 4JF,H = 5.7 Hz) ppm. – MS
((+)-ESI): m/z (%) = 304.1 (22) [M+2H]2+, 607.2 (100)
[M+H]+). – C30H32F2N8O4 (606.52): calcd. C 59.40, H
5.32, N, 18.47; found C 59.32, H 5.47, N 18.36.
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(3.36). – H NMR (400 MHz, CDCl3): δ = 8.14 (s, 1 H, 4-
H), 7.38−7.33 (m, 2 H, 2 × 9-H), 7.02−7.96 (m, 2 H, 2 × 10-
H), 4.63 (s, 2 H, 7-CH2), 4.52−4.46 (m, 4 H, 14-CH2, 7-
CH2), 1.45 (t, J = 7.1 Hz, 3 H, 18-CH3), 1.40 (t, J = 7.1 Hz,
3 H, 15-CH3) ppm. – 13C NMR (100 MHz, CDCl3): δ =
162.3 (d, 1JC,F = 245.4 Hz, C-11), 151.3 (C-6), 149.9 (C-16,
C=O), 148.2 (C-13, C=O), 146.0 (C-12, C=O), 138.1 (C-
Table 1. Crystallographic data for compound 11.
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3
Identification code
Empirical formula
Formula weight
i2t0902
C19H18BrFN4O5
481.28
2), 135.0 (d, JC,F = 3.1 Hz, C-8), 129.7 (d, JC,F = 8.0 Hz,
2
C-9), 126.8 (C-4), 115.5 (d, JC,F = 21.4 Hz, C-10), 111.5
(C-3), 99.1 (C-5), 64.4 (C-17, CH2), 64.3 (C-14, CH2), 45.4
Crystal size, mm3
Temperature T, K
0.23 × 0.10 × 0.09
(C-7), 14.3 (C-18, CH3), 14.2 (C-15, CH3) ppm. – 19F
200(2)
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NMR (376 MHz, CDCl3): δ = −120.1 (tt, JF,H = 8.9 Hz,
˚
Wavelength λ, A
0.71073
monoclinic; P21/n
4JF,H = 5.7 Hz) ppm. – MS ((+)-ESI): m/z (%) = 480.9 (8)
[M+H]+, 503.1 (100) [M+Na]+, 984.8 (48) [2M+Na]+. –
C19H18BrFN4O5 (481.04): calcd. C 47.42, H 3.77, N, 11.64;
found C 47.31, H 3.93, N 11.49.
Crystal system; space group
Unit cell dimensions
˚
a, A
4.901(1)
23.996(1)
16.943(1)
90.69(1)
1992.2(3)
2; 1.61
˚
b, A
˚
c, A
Diethyl {6,60-diamino-2,20-bis[(4-fluorobenzyl)amino]-
3,30-bipyridine-5,50-diyl} biscarbamate (4)
β, deg
3
˚
Volume V, A
Z; calculated density Dcalcd., g cm−3
Absorption coefficient µ(MoKα ), mm−1 2.1
Under argon a solution of 10 (10.00 g, 26.1 mmol) and
triethylamine (7.92 g, 78.3 mmol) in dry THF (100 mL)
at 60 ◦C was added to a suspension of NiCl2 (0.34 g,
2.6 mmol), triphenylphosphane (5.46 g, 20.8 mmol), pow-
dered Zn (5.12 g, 78.3 mmol), and triethylamine (7.92 g,
78.3 mmol) in dry THF (100 mL). The mixture was stirred
for 2 days at 60 ◦C, then the mixture was poured onto the
top of a glass column containing silica gel. The product
was eluted using a mixture of THF-diethyl ether (1 : 1).
2θ range for data collection, deg
Limiting indices hkl
6.22−55.99
±6, −26 → 31, −19 → 22
9380 / 4644 / 0.0549
4644 / 271
Reflections collected / unique / Rint
Data/ refined parameters
Final indices R1 / wR2 [I > 2σ(I)]
Funal indices R1 / wR2 (all data)
Goodness of fit on F2
0.0343 / 0.0740
0.0749 / 0.0991
0.804
Largest diff. peak / hole ∆ρfin
0.41 / −0.43
−3
˚
(max / min), e A