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I. Jarak et al. / European Journal of Medicinal Chemistry 46 (2011) 2807e2815
Hamidine) 9.12 (s, 2H, Hamidine) 8.03 (d, 2H, J ¼ 8.87 Hz, Harom.
)
(4C), 118.9 (2C), 116.8 (2C), 105.9 (2C); Anal. (C20H12N4O3)
Calcd.: C, 67.39; H, 3.39; N, 15.73; Found: C, 67.47; H, 3.52; N,
15.81.
7.989e7.995 (m, 1H, Hfuran5) 7.86 (d, 2H, J ¼ 8.84 Hz, Harom.) 7.56 (d,
1H, J ¼ 3.46 Hz, Hfuran3) 6.730e6.747 (m, 1H, Hfuran4); 13C NMR
(DMSO-d6) (d ppm): 158.2, 149.6, 139.1, 137.8, 135.8, 120.6 (2C),
114.8, 112.1 (2C), 107.7, 104.1; Anal. (C12H12ClN3O2 ꢀ H20) Calcd.: C,
51.18; H, 4.97; N, 14.81; Found: C, 50.99; H,5.18; N,14.81. method b.:
following the general procedure C, from 3 (1.51 g, 0.0071 mol) and
after recrystallization from water: 0.263 g (14%) of white crystals.
4.1.11. N,N0-di-(4-amidinophenyl)-(pyridine-2,6-di-yl)-carboxamide
hydrochloride (13)
Following the general procedure B, from 4 (0.8 g, 0.0059 mol) in
dry DMF (100 ml), 12 (0.57 g, 0.0028 mol) in dry THF (40 ml), and
Et3N (1.4 ml, 0.010 mol), after refluxing for 48 h and recrystalliza-
tion from methanol: 0.88 g (66%) of white powder. was obtai-
4.1.7. N-[4e(N0-Isopropylamidino)phenyl]-furan-2-yl-carboxamide
hydrochloride (6)
ned,.mp. >300 ꢂC (lit.6 ¼ 318 ꢂC); 1H NMR (DMSO-d6) (
d ppm):
Following the general procedure C, from 3 (1.0 g, 0.0047 mol) and
after recrystallization from methanol: 0.41 g (28%) of white crystals.
was obtained,mp 292e296 ꢂC; IR (KBr) (nmax/cmꢁ1): 3117, 2969,
11.79 (s, 2H, Hamide), 9.34 (s, 4H, Hamidine), 9.07 (s, 4H, Hamidine),
8.415 (d, 2H, Hpy, J ¼ 7.32 Hz), 8.33 (d, 5H, 4Harom.,1Hpy, J ¼ 8.64 Hz),
7.91 (d, 4H, Harom., J ¼ 8.65 Hz).
2854, 1678, 1666, 1621; 1H NMR (DMSO-d6) (
d ppm): 10.72 (s, 1H,
Hamide) 9.48 (d, 1H, J ¼ 7.98 Hz, Hamidine) 9.37 (s, 1H, Hamidine) 9.04 (s,
4.1.12. N,N0-di-[4e(N00-isopropyl)amidinophenyl]-(pyridine-2,6-di-
yl)-carboxamide hydrochloride (14)
Following the general procedure B, from 8 (1.5 g, 0.0085 mol) in
dry DMF (100 ml), 12 (0.86 g, 0.0042 mol) in dry THF (50 ml), and
Et3N (3 ml, 0.022 mol), after refluxing for 48 h and recrystallization
from ethanol: 1.25 g (53%) of white powder. was obtained mp
238e242 ꢂC; IR (KBr) (nmax/cmꢁ1): 3200, 3020, 1650, 1600; 1H NMR
1H, Hamidine) 8.01 (d, 2H, J ¼ 8.31 Hz, Harom.) 7.98 (s, 1H, Hfuran5) 7.73
(d, 2H, J ¼ 8.64 Hz, Harom.) 7.54 (d, 1H, J ¼ 3.33 Hz, Hfuran3
)
6.728e6.739 (m, 1H, Hfuran4) 4.02e4.09 (m, 1H, CHi-pr) 1.26 (d, 6H,
J ¼ 6.32, 2CH3 i-pr); 13C NMR (CD3OD) (
d ppm): 164.4, 159.2, 148.8,
147.5, 144.8, 130.2 (2C), 125.9, 121.8 (2C), 117.3, 113.7; Anal.
(C15H18ClN3O2) Calcd.: C, 58.53; H, 5.89; N,13.65; Found: C, 58.23; H,
5.89; N, 13.41.
(DMSO-d6) (d ppm): 11.91 (s, 2H, Hamide), 9.54 (d, 2H, Hamidine,
J ¼ 7.68 Hz), 9.43 (s, 2H, Hamidine), 9.08 (s, 2H, Hamidine), 8.28e8.41
(m, 7H, 4Harom., 3Hpy), 7.79 (d, 4H, Harom., J ¼ 8.97 Hz), 4.05e4.07
(m, 2H, CHi-pr), 1.27 (d, 12H, CH3 i-pr, J ¼ 6.32 Hz); 13C NMR (DMSO-
4.1.8. N,N0-di-(4-amidinophenyl)-(furan-2,5-di-yl)-carboxamide
hydrochloride (9)
Following the general procedure B, from 4 (1.23 g, 0.0091 mol) in
dry DMF (150 ml), 7 (0.8 g, 0.0041 mol) in dry THF (30 ml), and Et3N
(2.8 ml, 0.02 mol), after refluxing for 15 h and recrystallization from
water: 0.37 g (19.6%) of white powder was obtained,. mp >300 ꢂC;
d6) (d ppm): 162.8,161.3,149.1,143.1,139.9,129.1,126.0,124.0,120.6,
45.1, 21.4; Anal. (C27H33Cl2N7O2 ꢀ 3H2O) Calcd.: C, 52.94; H, 6.41; N,
16.01. Found: C, 52.59; H, 6.85; N, 16.20.
IR (KBr) (nmax/cmꢁ1): 3300,1660,1600; 1H NMR (DMSO-d6) (
d
ppm):
4.1.13. N,N0-di-(4-cyanobenzoyl)-(pyridine-2,6-di-yl)-amine (17)
Following the general procedure A, from 16 (2.96 g, 0.0018 mol)
in dry toluene (50 ml), 15 (0.72 g, 0.0071 mol) in dry THF (50 ml),
and Et3N (6.6 ml, 0.090 mol), after refluxing for 2.5 h and recrys-
tallization from the mixture of DMF and ethanol (1:1): 1.77 g (68%)
11.81 (s, 2H, Hamide) 9.27 (s, 4H, Hamidine) 8.95 (s, 4H, Hamidine) 8.32
(d, 4H, J ¼ 8.31 Hz, Harom.) 7.83 (d, 4H, J ¼ 8.31 Hz, Harom.) 7.46 (s, 2H,
Hfuran); 13C NMR (DMSO-d6) (
d ppm): 164.9 (2C), 156.0 (2C), 148.2
(2C), 143.7 (2C), 129.0 (4C), 122.8 (2C), 120.1 (4C), 117.4 (2C); Anal.
(C20H20Cl2N6O3 ꢀ 3H2O) Calcd.: C, 46.43; H, 5.06; N,16.34; Found: C,
46.75; H, 5.08; N, 16.70.
of white powder. was obtained mp 298-300 ꢂC; IR (KBr) (nmax
/
cmꢁ1): 3300, 2200, 1670, 1590; 1H NMR (DMSO-d6) (
d
ppm): 10.96
(s, 2H, Hamide), 8.11 (d, 4H, Harom., J ¼ 8.24 Hz), 8.01 (d, 4H, Harom.
,
4.1.9. N,N0-di-[4e(N00-isopropylamidino)phenyl]-(furan-2,5-di-yl)-
carboxamide hydrochloride (10)
J ¼ 8.24 Hz), 7.91 (s, 3H, Hpy); 13C NMR (DMSO-d6) (
d ppm): 164.9,
150.3, 140.4, 138.4, 132.6, 128.9, 118.4, 114.3, 111.7; Anal.
(C21H13N5O2) Calcd.: C, 68.66; H, 3.57; N, 19.06. Found: C, 68.52; H,
3.66; N, 19.17.
Following the general procedure B, from 8 (2.21 g, 0.012 mol) in
dry toluene (150 ml), 7 (1.0 g, 0.0052 mol) in dry toluene (50 ml),
and Et3N (0.9 ml, 0.006 mol), after refluxing for 14 h and recrys-
tallization from ethanol: 0.52 g (18.3%) of white powder. was
obtained,. mp >300 ꢂC; IR (KBr) (nmax/cmꢁ1): 3241, 3058, 2975,
4.1.14. N,N0-di-(4-amidinobenzoyl)-(pyridine-2,6-di-yl)-amine
hydrochloride (18)
2932, 1697, 1670, 1619; 1H NMR (DMSO-d6) (
d
ppm): 11.87 (s, 2H,
Following the general procedure C, from 17 (1.05 g, 0.0029 mol)
and after recrystallization from methanol: 0.24 (22%) of white
powder. was obtained, mp 224-228 ꢂC; IR (KBr) (nmax/cmꢁ1): 3200,
Hamide) 9.48 (d, 2H, J ¼ 7.64 Hz, Hamidine) 9.47 (s, 2H, Hamidine) 9.01
(s, 2H, Hamidine) 8.33 (d, 2H, J ¼ 7.64 Hz, Harom.) 7.72 (d, 4H,
J ¼ 8.65 Hz, Harom.) 7.44 (s, 2H, Hfuran) 4.03e4.07 (m, 2H, J ¼ 6.35 Hz,
1670, 1590; 1H NMR (DMSO-d6) (
d ppm): 10.91 (s, 2H, Hamide), 9.56
CHi-pr) 1.25 (d, 12H, J ¼ 6.32 Hz, CH3 i-pr); 13C NMR (DMSO-d6) (
d
(s, 4H, Hamidine), 9.33 (s, 4H, Hamidine), 8.16 (d, 4H, Harom.,
ppm): 161.4 (2C), 156.0 (2C), 148.3 (2C), 143.2 (2C), 129.1 (4C), 124.0
(2C), 120.1 (4C), 117.4 (2C), 45.0 (2C), 21.4 (4C); Anal.
(C26H32Cl2N6O3 ꢀ H2O) Calcd.: C, 55.22; H, 6.06; N, 14.86; Found:
55.41; H, 6.18; N, 14.98.
J ¼ 8.31 Hz), 7.89e7.97 (m, 7H, 4Harom., 3Hpy); 13C NMR (DMSO-d6)
(
d
ppm): Anal. (C21H21Cl2N7O2 ꢀ 2H2O) Calcd.: C, 49.42; H, 4.94; N,
17.21. Found: C, 49.49; H, 5.30; N, 17.15.
4.1.15. N,N0-di-[4e(N00-isopropyl)amidinobenzoyl]-(pyridine-2,6-
di-yl)-amine hydrochloride (19)
Following the general procedure C, from 17 (0.47 g, 0.0013 mol)
and after recrystallization from the mixture of ethyl acetate and
methanol (1:1): 0.16 g (28%) of white powder. was obtained, mp
230-234 ꢂC; IR (KBr) (nmax/cmꢁ1): 3380, 3040, 1650, 1620, 1600; 1H
4.1.10. N,N0-di-(4-cyanophenyl)-(furan-2,5-di-yl)-carboxamide (11)
Following the general procedure A, from 7 (1.0 g, 0.0052 mol)
in dry toluene (130 ml), 2 (1.22 g, 0.0103 mol) in dry toluene
(30 ml), and Et3N (3.5 ml, 0.025 mol), after refluxing for 14 h
and recrystallization from the mixture of DMF and water (1:1):
0.24 g (12.7%) of white powder. was obtained,.mp >300 ꢂC; IR
NMR (DMSO-d6) (d ppm): 11.91 (s, 2H, Hamide), 9.54 (d, 2H, Hamidine,
(KBr) (nmax/cmꢁ1): 2220, 1670, 1590; 1H NMR (DMSO-d6) (
d
J ¼ 7.68 Hz), 9.43 (s, 2H, Hamidine), 9.08 (s, 2H, Hamidine), 8.28e8.41
(m, 7H, 4Harom., 3Hpy), 7.79 (d, 4H, Harom., J ¼ 8.97 Hz), 4.05e4.07
(m, 2H, CHi-pr), 1.27 (d, 12H, CH3 i-pr, J ¼ 6.32 Hz); 13C NMR (DMSO-
ppm): 10.71 (s, 2H, Hamide) 7.985 (d, 4H, J ¼ 8.75 Hz, Harom.), 7.87
(d, 4H, J ¼ 8.73 Hz, Harom.) 7.55 (s, 2H, Hfuran); 13C NMR (DMSO-
d6) (
d
ppm): 155.8 (2C), 148.1 (2C), 142.4 (2C), 133.3 (4C), 120.3
d6) (d ppm): 162.8,161.3,149.1,143.1,139.9,129.1,126.0,124.0,120.6,