Pyrano[3,2-c]pyridones and Pyrano[3,2-c]quinolones
Journal of Medicinal Chemistry, 2008, Vol. 51, No. 8 2567
31.1, 24.3, 20.6; HRMS m/z (ESI) calcd for C20H21N3O2 (M +
Na+) 358.1531, found 358.1519.
57.4, 37.4, 29.9; HRMS m/z (ESI) calcd for C21H16N4O6 (M +
Na+) 443.0968, found 443.0966.
2-Amino-6,7-dimethyl-4-(3-nitrophenyl)-5-oxo-5,6-dihydro-
4H-pyrano[3,2-c]pyridine-3-carbonitrile (18): 97%; 1H NMR
(DMSO-d6) δ: 8.04 (d, J ) 7.7 Hz, 1H), 7.95 (s, 1H), 7.65–7.53
(m, 2H) 6.15 (s, 2H), 6.06 (s, 1H), 4.52 (s, 1H), 3.27 (s, 3H), 2.32
(s, 3H); 13C NMR (DMSO-d6) δ: 161.8, 159.9, 155.6, 149.1, 148.4,
147.6, 134.9, 130.3, 122.6, 122.1, 120.1, 105.0, 97.5, 56.6, 37.4,
31.1, 20.5; HRMS m/z (ESI) calcd for C17H14N4O4 (M + Na+)
361.0913, found 361.0909.
2-Amino-6-methyl-4-(3-nitrophenyl)-5-oxo-5,6-dihydro-4H-
pyrano[3,2-c]quinoline-3-carbonitrile(26): 77%; 1H NMR (DMSO-
d6) δ: 8.11–8.04 (m, 3H), 7.75–7.54 (m, 4H), 7.41–7.36 (m, 1H),
7.00 (s, 2H), 4.78 (s, 1H), 3.56 (s, 3H); 13C NMR (DMSO-d6) δ:
160.4, 160.0, 150.7, 149.9, 139.3, 134.0, 133.8, 132.4, 131.3, 128.4,
124.3, 122.9, 122.7, 119.4, 115.5, 113.1, 108.8, 56.9, 32.6, 29.8;
HRMS m/z (ESI) calcd for C20H14N4O4 (M + Na+) 397.0913, found
397.0917.
2-Amino-4-(3-bromophenyl)-7-methyl-5-oxo-4H,5H-pyrano-
[4,3-b]pyran-3-carbonitrile (19): 87%; H NMR (DMSO-d6) δ:
2-Amino-6-methyl-4-(2-nitrophenyl)-5-oxo-5,6-dihydro-4H-
pyrano[3,2-c]quinoline-3-carbonitrile (27): 73%; 1H NMR (DMSO-
d6) δ: 8.06–8.03 (m, 1H), 7.86–7.84 (m, 1H), 7.73–7.66 (m, 1H),
7.61–7.51 (m, 2H), 7.45–7.36 (m, 3H), 7.29 (s, 2H), 5.34 (s, 1H),
3.48 (s, 3H); 13C NMR (DMSO-d6) δ: 160.4, 160.1, 150.8, 150.0,
139.4, 134.0, 133.8, 132.4, 131.3, 128.5, 124.4, 122.8, 119.5, 115.3,
113.2, 108.8, 57.0, 32.6, 29.8; HRMS m/z (ESI) calcd for
C20H14N4O4 (M + Na+) 397.0913, found 397.0910.
2-Amino-6-methyl-5-oxo-4-(4-pyridinyl)-5,6-dihydro-4H-pyr-
ano[3,2-c]quinoline-3-carbonitrile (28): 79%; 1H NMR (DMSO-
d6) δ: 8.45 (d, J ) 8.5 Hz, 2H), 8.03 (d, J ) 8.0 Hz, 1H), 7.73–7.67
(m, 1H), 7.54 (d, J ) 7.5 Hz, 1H), 7.41–7.22 (m, 5H), 4.55 (s,
1H), 3.52 (s, 3H); 13C NMR (DMSO-d6) δ: 160.3, 159.7, 153.1,
151.2, 150.4, 150.2, 139.3, 132.3, 123.4, 122.9, 119.8, 115.3, 113.1,
107.9, 57.0, 37.6, 29.8; HRMS m/z (ESI) calcd for C19H14N4O2
(M + Na+) 353.1014, found 353.1017.
2-Amino-6-methyl-5-oxo-4-(3-pyridinyl)-5,6-dihydro-4H-pyr-
ano[3,2-c]quinoline-3-carbonitrile (29): 81%; 1H NMR (DMSO-
d6) δ: 8.51 (d, J ) 3.6 Hz, 1H), 8.40 (m, 1H) 8.05 (m, 1H),
7.72–7.52 (m, 3H), 7.38–7.27 (m, 2H), 7.10 (s, 2H), 4.62 (s, 1H),
3.53 (s, 3H); 13C NMR (DMSO-d6) δ: 160.5, 159.8, 151.2, 149.8,
148.6, 140.1, 139.5, 135.5, 132.2, 124.4, 123.0, 122.6, 119.7, 115.3,
113.3, 108.7, 58.2, 35.7, 29.7; HRMS m/z (ESI) calcd for
C19H14N4O2 (M + Na+) 353.1014, found 453.1018.
1
7.43 (d, J ) 8.0 Hz, 1H), 7.38 (s, 1H), 7.32–7.27 (m, 1H), 7.21 (d,
J ) 8.0 Hz, 1H), 7.15 (s, 2H), 6.26 (s, 1H), 4.34 (s, 1H), 2.22 (s,
3H); 13C NMR (DMSO-d6) δ: 163.7, 161.9, 159.1, 158.8, 146.8,
131.3, 130.8, 130.5, 127.3, 122.1, 119.5, 100.6, 98.5, 58.1, 36.6,
19.7; HRMS m/z (ESI) calcd for C16H11BrN2O3 (M + Na+)
380.9845, found 380.9839.
2-Amino-6-(3,4-dimethoxyphenethyl)-7-methyl-5-oxo-4-(3,4,5-
trimethoxyphenyl)-5,6-dihydro-4H-pyrano[3,2-c]pyridine-3-car-
1
bonitrile (20): 80%; H NMR (DMSO-d6) δ: 6.90 (s, 2H), 6.83
(d, J ) 8.5 Hz, 1H), 6.69–6.63 (m, 2H), 6.52 (s, 2H),5.89 (s, 1H),
4.41 (s, 1H), 4.13–3.98 (m, 2H), 3.74 (s, 6H), 3.71 (s, 3H), 3.67
(s, 3H), 3.65 (s, 3H), 2.86–2.70 (m, 2H), 2.19 (s, 3H); 13C NMR
(DMSO-d6) δ: 161.6, 160.0, 155.6, 153.4, 149.5, 148.4, 147.6,
141.0, 137.4, 131.4, 121.3, 120.5, 113.6, 112.9, 106.6, 105.6, 97.6,
60.5, 58.4, 56.5, 56.3, 56.1, 40.1, 37.2, 33.3, 20.0; HRMS m/z (ESI)
calcd for C29H31N3O7 (M + Na+) 556.2060, found 556.2057.
2-Amino-6-methyl-5-oxo-4-phenyl-5,6-dihydro-4H-pyrano[3,2-
c]quinoline-3-carbonitrile (21): 78%; 1H NMR (DMSO-d6) δ: 8.06
(d, J ) 7.6 Hz, 1H), 7.70–7.66 (m, 1H), 7.52 (d, J ) 7.6 Hz, 1H),
7.40–7.18 (m, 6H), 6.98 (s, 2H), 4.56 (s, 1H), 3.55 (s, 3H); 13C
NMR (DMSO-d6) δ: 160.5, 159.6, 150.9, 144.9, 139.4, 132.1, 128.8,
128.0, 127.2, 122.9, 122.8, 122.6, 119.9, 115.3, 113.4, 109.8, 59.2,
37.8, 29.8; HRMS m/z (ESI) calcd for C20H15N3O2 (M + Na+)
352.1062, found 352.1058.
2-Amino-4-(2-furyl)-6-methyl-5-oxo-5,6-dihydro-4H-pyrano[3,2-
c]quinoline-3-carbonitrile(30): 75%; 1H NMR (DMSO-d6) δ: 8.04
(d, J ) 8.0 Hz, 1H), 7.73–7.67 (m, 1H), 7.56 (d, J ) 7.6 Hz, 1H),
7.41–7.34 (m, 2H), 6.93 (s, 2H), 6.32 (s, 1H), 6.14 (d, J ) 6.1 Hz,
1H), 4.72 (s, 1H), 3.60 (s, 3H); 13C NMR (DMSO-d6) δ: 160.4,
155.9, 151.5, 142.3, 142.1, 139.4, 132.1, 122.9, 122.5, 119.5, 115.2,
113.4, 110.9, 107.2, 106.2, 56.7, 31.8, 29.9; HRMS m/z (ESI) calcd
for C18H13N3O3 (M + Na+) 342.0855, found 342.0851.
2-Amino-6-methyl-5-oxo-4-(3,4,5-trimethoxyphenyl)-5,6-dihy-
dro-4H-pyrano[3,2-c]quinoline-3-carbonitrile (22): 86%; 1H
NMR (DMSO-d6) δ: 8.03 (d, J ) 8.0 Hz, 1H), 7.72–7.66 (m, 1H),
7.55 (d, J ) 7.6 Hz, 1H), 7.40–7.35 (m, 1H), 7.14 (s, 2H), 6.51 (s,
2H), 4.53 (s, 1H), 3.71 (s, 6H), 3.64 (s, 3H); 13C NMR (DMSO-
d6) δ: 160.6, 159.6, 153.4, 150.8, 140.4, 139.3, 137.5, 132.2, 122.9,
122.7, 120.1, 115.4, 113.3, 109.4, 105.9, 60.5, 58.6, 56.6, 38.2,
29.9; HRMS m/z (ESI) calcd for C23H21N3O5 (M + Na+) 442.1379,
found 442.1389.
2-Amino-4-(3-hydroxy-4-methoxyphenyl)-6-methyl-5-oxo-5,6-
dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile (23): 82%; 1H
NMR (DMSO-d6) δ: 8.90 (s, 1H), 8.00 (d, J ) 8.0 Hz, 1H),
7.72–7.67 (m, 1H), 7.55 (d, J ) 7.6 Hz, 1H), 7.41–7.36 (m, 1H),
7.23 (s, 2H), 6.79 (d, J ) 6.8 Hz, 1H), 6.61 (s, 2H), 4.37 (s, 1H),
3.71 (s, 3H), 3.55 (s, 3H); 13C NMR (DMSO-d6) δ: 160.3, 159.3,
150.4, 147.1, 146.8, 139.1, 137.6, 132.0, 122.8, 120.4, 118.7, 115.5,
115.1, 113.2, 112.7, 110.0, 58.8, 56.4, 37.2, 29.8; HRMS m/z (ESI)
calcd for C21H17N3O4 (M + Na+) 398.1117, found 398.1123.
2-Amino-4-(4-hydroxy-3-methoxyphenyl)-6-methyl-5-oxo-5,6-
dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile (24): 84%; 1H
NMR (DMSO-d6) δ:8.70 (s, 1H), 8.03 (d, J ) 7.5 Hz, 1H),
7.70–7.65 (m, 1H), 7.53 (d, J ) 7.6 Hz, 1H), 7.39–7.34 (m, 1H),
7.08 (s, 2H), 6.84 (s, 1H), 6.79 (d, J ) 8.2 Hz, 1H), 6.60–6.57 (m,
1H), 4.47 (s, 1H), 3.73 (s, 3H), 3.55 (s, 3H); 13C NMR (DMSO-
d6) δ: 160.5, 159.5, 150.4, 147.7, 146.3, 139.3, 136.0, 132.3, 122.7,
120.4, 116.2, 115.2, 113.3, 113.1, 110.0, 59.0, 56.4, 37.1, 29.8;
HRMS m/z (ESI) calcd for C21H17N3O4 (M + Na+) 398.1117, found
398.1119.
2-Amino-6-methyl-4-(5-methyl-2-furyl)-5-oxo-5,6-dihydro-
1
4H-pyrano[3,2-c]quinoline-3-carbonitrile (31): 78%; H NMR
(DMSO-d6) δ: 8.03 (d, J ) 8.0 Hz, 1H), 7.71–7.57 (m, 2H),
7.40–7.35 (m, 1H), 7.01 (s, 2H), 5.99–5.91 (m, 2H), 4.64 (s, 1H),
3.60 (s, 3H), 2.17 (s, 3H); 13C NMR (DMSO-d6) δ: 160.4, 159.7,
151.5, 151.5, 145.0, 139.5, 132.5, 131.2, 129.3, 128.8, 123.1, 122.8,
119.6, 115.4, 113.1, 108.3, 56.9, 36.4, 29.9; HRMS m/z (ESI) calcd
for C19H15N3O3 (M + Na+) 356.1011, found 356.1022.
2-Amino-4-(2,3-dichlorophenyl)-6-methyl-5-oxo-5,6-dihydro-
1
4H-pyrano[3,2-c]quinoline-3-carbonitrile (32): 95%; H NMR
(DMSO-d6) δ: 8.05 (d, J ) 8.0 Hz, 1H), 7.75–7.70 (m, 1H), 7.55
(d, J ) 8.8 Hz, 1H), 7.48–7.38 (m, 2H), 7.27–7.14 (m, 4H), 5.15
(s, 1H), 3.52 (s, 3H); 13C NMR (DMSO-d6) δ: 160.4, 159.6, 151.5,
145.0, 139.5, 132.5, 131.2, 129.3, 128.8, 123.1, 122.8, 122.7, 119.6,
115.6, 115.4, 113.1, 108.3, 56.9, 36.4, 29.9; HRMS m/z (ESI) calcd
for C20H13Cl2N3O2 (M + Na+) 420.0283, found 420.0284.
2-Amino-4-(2,6-dichlorophenyl)-6-methyl-5-oxo-5,6-dihydro-
1
4H-pyrano[3,2-c]quinoline-3-carbonitrile (33): 88%; H NMR
(DMSO-d6) δ: 8.05 (d, J ) 8.0 Hz, 1H), 7.72–7.67 (m, 1H),
7.55–7.21 (m, 5H), 6.91 (bs, 2H), 5.62 (s, 1H), 3.52 (s, 3H); 13C
NMR (DMSO-d6) δ: 160.1, 139.6, 137.0, 132.4, 132.2, 129.6, 129.4,
122.8, 122.6, 122.4, 119.1, 115.1, 113.1, 106.7, 55.2, 34.6, 29.5;
HRMS m/z (ESI) calcd for C20H13Cl2N3O2 (M + Na+) 420.0283,
found 420.0280.
2-Amino-4-(4-hydroxy-3-methoxy-5-nitrophenyl)-6-methyl-5-
oxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carbonitrile (25):
89%; 1H NMR (DMSO-d6) δ: 10.20 (s, 1H), 8.03 (d, J ) 8.0 Hz,
1H), 7.73–7.67 (m, 1H), 7.55 (d, J ) 7.6 Hz, 1H), 7.41–7.36 (m,
1H), 7.23 (s, 4H), 4.61 (s, 1H), 3.85 (s, 3H), 3.54 (s, 3H); 13C
NMR (DMSO-d6) δ: 160.5, 159.7, 150.9, 149.9, 142.3, 139.3, 137.4,
135.8, 132.3, 122.7, 120.0, 117.2, 115.4, 114.8, 113.2, 108.7, 57.9,
2-Amino-4-(3,4-dichlorophenyl)-6-methyl-5-oxo-5,6-dihydro-
1
4H-pyrano[3,2-c]quinoline-3-carbonitrile (34): 97%; H NMR
(DMSO-d6) δ: 8.03 (d, J ) 8.0 Hz, 1H), 7.72–7.67 (m, 1H),
7.55–7.19 (m, 7H), 4.58 (s, 1H), 3.52 (s, 3H); 13C NMR (DMSO-
d6) δ: 160.4, 159.5, 150.9, 145.9, 139.4, 132.5, 131.4, 131.1, 130.2,