H.H. Jardosh, M.P. Patel / European Journal of Medicinal Chemistry 65 (2013) 348e359
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carboxylate (7f). IR (KBr, nmax, cmꢀ1): 3396 and 3276 (asym. and sym.
str. of eNH2), 2986 (Ar CeH str.), 1647 and 1698 (C]O str.); 1H NMR
H4), 5.01 (d, 1H, J ¼ 11.6 Hz, NeCH2CH]CH-cis), 5.08 (m, 1H, HCe
(CH3)2), 5.79 (m, 1H, CH]CH2), 7.28e8.83 (m, 10H, AreH þ NH2),
(400 MHz, DMSO-d6)
d
ppm: 0.78, (d, 3H, J ¼ 6.4 Hz, HCe(CH3)2),
11.74 (s, 1H, NH); 13C NMR (APT) (100 MHz, DMSO-d6)
d ppm: 21.07,
0.92 (s, 6H, 2ꢃ CH3 of dimedone ring), 1.21 (d, 3H, J ¼ 6.4 Hz, HCe
(CH3)2), 1.84e2.18 (m, 4H, 2ꢃ CH2 of dimedone ring), 4.61 (d, 2H,
J ¼ 13.6 Hz, NeCH2), 4.74 (d, 1H, J ¼ 17.6 Hz, NeCH2CH]CH-trans),
4.81 (s,1H, CH, quinolone H4), 5.01 (d,1H, J ¼ 9.2 Hz, NeCH2CH]CH-
cis), 5.05 (m, 1H, HCe(CH3)2), 5.78 (m, 1H, CH]CH2), 7.21e8.87 (m,
11H, AreH þ NH2), 11.79 (s, 1H, NH); 13C NMR (APT) (100 MHz,
22.24, (2ꢃ CH3, HCe(CH3)2), 22.84 (CH2), 24.77 (CH2), 29.56 (CH3),
35.67 (quinolone C4), 36.54 (CH2eCO), 43.98 (allylic NeCH2eCH),
65.21 (HCe(CH3)2), 74.23 (CeCOOCHe(CH3)2), 109.82, 114.83,
116.12, 120.44, 120.91, 122.35, 122.54, 128.37, 130.92, 131.14, 133.11,
133.24, 136.57, 138.83, 150.72, 150.80, 153.58, 154.67 (18C, Are
C þ allylic C]C), 159.86 (C]O), 165.70 (C]O), 169.75 (C]O),
195.20 (C]O); Anal. Calcd. for C32H33N5O5 (567.63 g/mol): C, 67.71;
H, 5.86; N, 12.34; Found: C, 67.54; H, 6.23; N, 12.32.
DMSO-d6)
d
ppm: 20.66, 22.39, (2ꢃ CH3, HCe(CH3)2), 22.80, 25.62
(2ꢃ CH3 of dimedone ring), 31.89 (CH2), 35.81 (quinolone C4), 37.78
(C(CH3)2), 43.91 (allylic NeCH2eCH), 49.92 (CH2eCO), 65.21 (HCe
(CH3)2), 74.17 (CeCOOCHe(CH3)2), 110.90, 114.81, 116.30, 117.15,
120.52, 121.11, 122.46, 128.84, 129.80, 131.83, 133.44, 138.15, 138.50,
142.92, 150.70, 153.15, 154.44, 155.32 (18C, AreC þ allylic C]C),
160.19 (C]O), 165.76 (C]O), 168.97 (C]O), 195.25 (C]O); Anal.
Calcd. for C33H35N5O5 (581.66 g/mol): C, 68.14; H, 6.07; N, 12.04;
Found: C, 68.10; H, 6.34; N, 11.76.
6.1.2.10. Methyl 1-allyl-20-amino-10-(isonicotinamido)-6,70,70-trimet
hyl-2,50-dioxo-1,10,2,40,50,60,70,80-octahydro-3,40-biquinoline-30-
carboxylate (7j). IR (KBr, nmax, cmꢀ1): 3386 and 3210 (asym. and
sym. str. of eNH2), 3047 (Ar CeH str.), 1651 and 1697 (C]O str.); 1H
NMR (400 MHz, DMSO-d6)
d ppm: 0.76 (s, 3H, CH3 of dimedone
ring), 0.90 (s, 3H, CH3 of dimedone ring), 1.85e2.21 (m, 4H, 2ꢃ CH2
of dimedone ring), 2.71 (s, 3H, CH3), 3.47 (s, 3H, COOCH3), 4.57 (d,
2H, J ¼ 14.4 Hz, NeCH2), 4.75 (d, 1H, J ¼ 16.4 Hz, NeCH2CH]CH-
trans), 4.86 (s, 1H, CH, quinolone H4), 5.01 (d, 1H, J ¼ 11.6 Hz, Ne
CH2CH]CH-cis), 5.80 (m, 1H, CH]CH2), 7.31e8.82 (m, 10H, Are
H þ NH2), 11.82 (s, 1H, NH); 13C NMR (APT) (100 MHz, DMSO-d6)
6.1.2.7. Methyl 1-allyl-20-amino-10-(isonicotinamido)-6-methyl-2,50-
dioxo-1,10,2,40,50,60,70,80-octahydro-3,40-biquinoline-30-carboxylate
(7g). IR (KBr, nmax, cmꢀ1): 3386 and 3210 (asym. and sym. str. of e
NH2), 3048 (Ar CeH str.), 1650 and 1695 (C]O str.); 1H NMR
(400 MHz, DMSO-d6)
d
ppm: 1.53e2.73 (m, 9H, 3ꢃ CH2 of cyclo-
d
ppm: 24.59, 25.71 (2ꢃ CH3 of dimedone ring), 29.58 (CH3), 31.95
hexenone ring þ CH3), 3.42 (s, 3H, COOCH3), 4.72 (d, 2H, J ¼ 12.4 Hz,
NeCH2), 4.85 (d, 1H, J ¼ 17.6 Hz, NeCH2CH]CH-trans), 4.94 (s, 1H,
CH, quinolone H4), 5.05 (d, 1H, J ¼ 10.4 Hz, NeCH2CH]CH-cis), 5.81
(m, 1H, CH]CH2), 7.12e8.85 (m, 10H, AreH þ NH2), 11.77 (s, 1H,
(CH2), 35.64 (quinolone C4), 37.77 (C(CH3)2), 44.21 (allylic NeCH2e
CH), 49.86 (CH2eCO), 50.51 (COOCH3), 73.78 (CeCOOCH3), 109.63,
113.66, 116.98, 122.07, 122.36, 122.55, 125.33, 126.26, 127.98, 132.74,
134.70, 137.21, 138.83, 150.76, 152.09, 153.71, 154.82, 157.73 (18C,
AreC þ allylic C]C), 160.14 (C]O), 165.62 (C]O), 168.91 (C]O),
195.07 (C]O); Anal. Calcd. for C32H33N5O5 (567.63 g/mol): C, 67.71;
H, 5.86; N, 12.34; Found: C, 67.90; H, 5.69; N, 12.42.
NH); 13C NMR (APT) (100 MHz, DMSO-d6)
d ppm: 21.06 (CH2), 24.74
(CH2), 27.81 (CH3), 35.06 (quinolone C4), 36.62 (CH2eCO), 44.17
(allylic NeCH2eCH), 50.51 (COOCH3), 74.15 (CeCOOCH3), 110.93,
111.12, 116.28, 116.47, 118.37, 121.52, 122.31, 122.50, 132.97, 133.54,
134.56, 137.16, 138.78, 150.64, 150.95, 154.45, 154.57, 155.25 (18C,
AreC þ allylic C]C), 159.98 (C]O), 165.74 (C]O), 169.76 (C]O),
195.20 (C]O); Anal. Calcd. for C30H29N5O5 (539.58 g/mol): C,
66.78; H, 5.42; N, 12.98; Found: C, 67.10; H, 5.13; N, 12.82.
6.1.2.11. Ethyl 1-allyl-20-amino-10-(isonicotinamido)-6,70,70-trimeth
yl-2,50-dioxo-1,10,2,40,50,60,70,80-octahydro-3,40-biquinoline-30-carbox-
ylate (7k). IR (KBr, nmax, cmꢀ1): 3392 and 3285 (asym. and sym. str.
of eNH2), 3048 (Ar CeH str.), 1650 and 1695 (C]O str.); 1H NMR
(400 MHz, DMSO-d6)
d ppm: 0.78 (s, 3H, CH3 of dimedone ring),
6.1.2.8. Ethyl 1-allyl-20-amino-10-(isonicotinamido)-6-methyl-2,50-
dioxo-1,10,2,40,50,60,70,80-octahydro-3,40-biquinoline-30-carboxylate
(7h). IR (KBr, nmax, cmꢀ1): 3394 and 3286 (asym. and sym. str. of e
NH2), 3047 (Ar CeH str.), 1652 and 1696 (C]O str.); 1H NMR
0.91 (s, 3H, CH3 of dimedone ring), 1.11 (t, 3H, J1 ¼ 12.4, J2 ¼ 6.4 Hz,
OCH2CH3), 1.84e2.19 (m, 4H, 2ꢃ CH2 of dimedone ring), 2.73 (s,
3H, CH3), 3.91 (q, 2H, J1 ¼ 7.6, J2 ¼ 6.4 Hz, OCH2CH3), 4.56 (d,
2H, J ¼ 15.2 Hz, NeCH2), 4.76 (d, 1H, J ¼ 17.2 Hz, NeCH2CH]CH-
trans), 4.85 (s, 1H, CH, quinolone H4), 5.00 (d, 1H, J ¼ 11.6 Hz, Ne
CH2CH]CH-cis), 5.80 (m, 1H, CH]CH2), 7.12e8.81 (m, 10H, Are
H þ NH2), 11.81 (s, 1H, NH); 13C NMR (APT) (100 MHz, DMSO-d6)
(400 MHz, DMSO-d6)
d
ppm: 1.07 (t, 3H, J1 ¼ 13.6, J2 ¼ 7.2 Hz,
OCH2CH3), 1.53e2.74 (m, 9H, 3ꢃ CH2 of cyclohexenone ring þ CH3),
3.92 (q, 2H, J1 ¼ 7.2, J2 ¼ 6.8 Hz, OCH2CH3) 4.74 (d, 2H, J ¼ 15.2 Hz,
NeCH2), 4.86 (d, 1H, J ¼ 17.6 Hz, NeCH2CH]CH-trans), 4.98 (s, 1H,
CH, quinolone H4), 5.08 (d, 1H, J ¼ 11.6 Hz, NeCH2CH]CH-cis), 5.82
(m, 1H, CH]CH2), 7.31e8.84 (m, 10H, AreH þ NH2), 11.76 (s, 1H,
d
ppm: 14.98, 25.66 (2ꢃ CH3 of dimedone ring), 29.52 (CH3), 30.54
(OCH2CH3), 31.95 (CH2), 35.81 (quinolone C4), 37.76 (C(CH3)2),
44.05 (allylic NeCH2eCH), 49.91 (CH2eCO), 58.54 (OCH2CH3),
73.92 (CeCOOCH2CH3),109.82,110.85,116.22,118.24,121.38,122.37,
122.50, 133.05, 133.21, 133.70, 137.72, 137.96, 138.82, 150.70, 150.74,
153.59, 154.47, 154.76 (18C, AreC þ allylic C]C), 160.15 (C]O),
165.61 (C]O), 168.92 (C]O), 195.08 (C]O); Anal. Calcd. for
NH); 13C NMR (APT) (100 MHz, DMSO-d6)
d ppm: 20.97 (CH2), 24.71
(CH2), 28.21 (OCH2CH3), 29.62 (CH3), 35.54 (quinolone C4), 36.43
(CH2eCO), 44.11 (allylic NeCH2eCH), 58.54 (COOCH2CH3), 73.84
(CeCOOCH2CH3), 110.92, 111.13, 116.27, 116.48, 118.35, 121.53,
122.31, 122.50, 132.98, 133.56, 134.52, 137.15, 138.72, 150.63, 150.96,
154.45, 154.57, 155.26 (18C, AreC þ allylic C]C), 160.01 (C]O),
165.73 (C]O), 169.76 (C]O), 195.21 (C]O); Anal. Calcd. for
C33H35N5O5 (581.66 g/mol): C, 68.14; H, 6.07; N, 12.04; Found: C,
67.80; H, 6.19; N, 11.98.
C
31H31N5O5 (553.61 g/mol): C, 67.26; H, 5.64; N, 12.65; Found: C,
6.1.2.12. Isopropyl 1-allyl-20-amino-10-(isonicotinamido)-6,70,70-trim
ethyl-2,50-dioxo-1,10,2,40,50,60,70,80-octahydro-3,40-biquinoline-30-
carboxylate (7l). IR (KBr, nmax, cmꢀ1): 3394 and 3279 (asym. and
sym. str. of eNH2), 2992 (Ar CeH str.), 1647 and 1696 (C]O str.); 1H
67.33; H, 5.46; N, 12.49.
6.1.2.9. Isopropyl 1-allyl-20-amino-10-(isonicotinamido)-6-methyl-2,
50-dioxo-1,10,2,40,50,60,70,80-octahydro-3,40-biquinoline-30-carboxylate
(7i). IR (KBr, nmax, cmꢀ1): 3394 and 3279 (asym. and sym. str. of e
NH2), 2992 (Ar CeH str.), 1647 and 1696 (C]O str.); 1H NMR
NMR (400 MHz, DMSO-d6)
d
ppm: 0.78 (d, 3H, J ¼ 6.4 Hz, HCe
(CH3)2), 0.93 (s, 6H, 2ꢃ CH3 of dimedone ring), 1.23 (d, 3H,
J ¼ 6.4 Hz, HCe(CH3)2), 1.85e2.19 (m, 4H, 2ꢃ CH2 of dimedone
ring), 2.37 (s, 3H, CH3), 4.62 (d, 2H, J ¼ 13.6 Hz, NeCH2), 4.76 (d, 1H,
J ¼ 17.6 Hz, NeCH2CH]CH-trans), 4.85 (s, 1H, CH, quinolone H4),
5.00 (d, 1H, J ¼ 9.2 Hz, NeCH2CH]CH-cis), 5.03 (m, 1H, HCe
(CH3)2), 5.79 (m, 1H, CH]CH2), 7.23e8.89 (m, 10H, AreH þ NH2),
(400 MHz, DMSO-d6)
d
ppm: 0.81, (d, 3H, J ¼ 6.4 Hz, HCe(CH3)2),
1.12 (d, 3H, J ¼ 6.4 Hz, HCe(CH3)2), 1.52e2.75 (m, 9H, 3ꢃ CH2 of
cyclohexenone ring þ CH3), 4.71 (d, 2H, J ¼ 15.2 Hz, NeCH2), 4.84
(d, 1H, J ¼ 17.6 Hz, NeCH2CH]CH-trans), 4.96 (s, 1H, CH, quinolone