O. Galayev et al. / European Journal of Medicinal Chemistry 105 (2015) 171e181
177
2.87 (m, 2H), 7.00 (t, J ¼ 7.2 Hz, 1H), 7.04 (s, 1H), 7.11 (t, J ¼ 7.2 Hz,
1H), 7.45 (d, J ¼ 7.8 Hz, 1H), 7.55 (d, J ¼ 7.8 Hz, 1H), 7.84 (s, 1H), 9.68
4.2.3.3. 6-[3-(Dimethylamino)prop-2-enoyl]-7-hydroxy-8-methyl-4-
propyl-2H-chromen-2-one (28). Yield 84%, mp 197e198 ꢀC. 1H NMR
(bs, 1H), 11.31 (s, 1H). 13C NMR (100 MHz, DMSO-d6):
d
161.56,
(400 MHz, DMSO-d6):
d
1.03 (t, 3H, J ¼ 7.2 Hz), 1.69 (m, 2H), 2.17 (s,
154.96, 150.46, 148.49, 136.97, 135.04, 129.10, 123.36, 121.93, 120.56,
119.69, 119.44, 118.35, 113.47, 112.93, 111.75, 102.74, 25.48, 24.20,
21.89, 21.50, 9.58. Calcd. for C22H19NO3: C, 76.50; H, 5.54; N, 4.06;
Found: C, 76.59; H, 5.68; N, 4.01%.
3H), 2.85 (t, 2H, J ¼ 7.2 Hz), 3.07 (s, 3H), 3.24 (s, 3H), 5.95 (d, 1H,
J ¼ 12.0 Hz), 6.10 (s, 1H), 7.97 (d, 1H, J ¼ 12.0 Hz), 7.98 (s, 1H), 15.35
(br s, 1H). 13C NMR (100 MHz, DMSO-d6): 187.10, 166.19, 161.17,
160.29, 160.01, 153.68, 125.88, 121.32, 118.15, 117.09, 110.65, 93.26,
42.15, 33.16, 21.32, 14.16, 12.35, 8.09. Calcd. for C18H21NO4: C, 68.55;
H, 6.71; N, 4.44; Found: C, 68.69; H, 6.82; N, 4.38%.
4.2.2.7. 6-(6-Fluoro-1H-indol-2-yl)-7-hydroxy-4,8-dimethyl-2H-
chromen-2-one (23). Yield 85%, mp 233e234 ꢀC. 1H NMR
(400 MHz, DMSO-d6)
d
2.31 (s, 3H), 2.47 (s, 3H), 6.21 (s, 1H), 6.94 (t,
4.2.3.4. 4-Butyl-6-[3-(dimethylamino)prop-2-enoyl]-7-hydroxy-8-
J ¼ 7.2 Hz, 1H), 7.03 (s, 1H), 7.31 (d, J ¼ 7.8 Hz, 1H), 7.44 (m, 1H), 7.88
methyl-2H-chromen-2-one (29). Yield 63%, mp 185e186 ꢀC. 1H NMR
(s, 1H), 9.93 (bs, 1H), 11.43 (s, 1H). 13C NMR (100 MHz, DMSO-d6):
(400 MHz, DMSO-d6):
d
0.95 (t, 3H, J ¼ 7.2 Hz), 1.41 (m, 2H), 1.59 (m,
d
161.41, 156.83, 154.98, 152.92, 137.44, 134.32, 129.79, 122.89,
2H), 2.12 (s, 3H), 2.83 (t, 2H, J ¼ 7.2 Hz), 3.05 (s, 3H), 3.25 (s, 3H),
5.94 (d, 1H, J ¼ 12.0 Hz), 6.11 (s, 1H), 7.95 (s, 1H), 7.97 (d, 1H,
J ¼ 12.0 Hz), 15.30 (br s, 1H). 13C NMR (100 MHz, DMSO-d6):
118.85, 114.10, 113.91, 113.37, 112.31, 110.78, 105.73, 105.49, 103.53,
19.61, 10.26. Calcd. for C19H14FNO3: C, 70.58; H, 4.36; N, 4.33;
Found: C, 70.71; H, 4.47; N, 4.24%.
d
186.96,166.13,162.19,160.22,156.95,153.80,125.73,119.15,117.83,
115.14, 114.32, 93.49, 41.95, 32.73, 27.30, 22.31, 14.12, 12.89, 8.11.
Calcd. for C19H23NO4: C, 69.28; H, 7.07; N, 4.25; Found: C, 69.17; H,
6.98; N, 4.31%.
4.2.2.8. 7-Hydroxy-4,8-dimethyl-6-(7-methyl-1H-indol-2-yl)-2H-
chromen-2-one (24). Yield 85%, mp 224e225 ꢀC. 1H NMR (400 MHz,
DMSO-d6)
6.84e6.96 (m, 3H), 7.38 (d, J ¼ 6.8 Hz, 1H), 7.87 (s, 1H), 9.83 (bs, 1H),
10.93 (s, 1H). 13C NMR (100 MHz, DMSO-d6):
160.89, 156.29,
d 2.32 (s, 3H), 2.49 (s, 3H), 2.55 (s, 3H), 6.23 (s, 1H),
4.2.3.5. 6-[3-(Dimethylamino)prop-2-enoyl]-7-hydroxy-3,4,8-
d
trimethyl-2H-chromen-2-one (30). Yield 81%, mp 205e206 ꢀC. 1H
154.49, 152.23,136.47, 134.70,128.73,123.00,122.67,120.98,120.04,
118.69, 118.25, 113.27, 113.01, 111.55, 103.45, 19.05, 17.79, 9.59. Calcd.
for C20H17NO3: C, 75.22; H, 5.37; N, 4.39; Found: C, 75.08; H, 5.31; N,
4.48%.
NMR (400 MHz, DMSO-d6): d 2.07 (s, 3H), 2.14 (s, 3H), 2.39 (s, 3H),
3.07 (s, 3H), 3.19 (s, 3H), 5.98 (d, 1H, J ¼ 12.0 Hz), 7.91 (s,1H), 7.94 (d,
1H, J ¼ 12.0 Hz), 14.80 (br s, 1H). 13C NMR (100 MHz, DMSO-d6):
d
189.74, 163.51, 161.27, 156.32, 153.39, 147.51, 122.97, 117.66, 116.61,
111.97, 111.79, 89.68, 45.59, 38.13, 15.35, 13.29, 7.87. Calcd. for
C17H19NO4: C, 67.76; H, 6.36; N, 4.65; Found: C, 67.79; H, 6.48; N,
4.59%.
4.2.2.9. 6-(5-Bromo-1H-indol-2-yl)-7-hydroxy-4,8-dimethyl-2H-
chromen-2-one (25). Yield 84%, mp 248e249 ꢀC. 1H NMR
(300 MHz, DMSO-d6) d 2.32 (s, 3H), 2.48 (s, 3H), 6.23 (s, 1H), 7.04 (s,
1H), 7.20 (d, J ¼ 8.7 Hz, 1H), 7.42 (d, J ¼ 8.7 Hz, 1H), 7.75 (s, 1H), 7.90
4.2.3.6. 8-[3-(Dimethylamino)prop-2-enoyl]-7-hydroxy-6-methyl-
(s, 1H), 9.75 (bs, 1H), 11.57 (s, 1H). 13C NMR (100 MHz, DMSO-d6):
2,3-dihydrocyclopenta[c]chromen-4(1H)-one (31). Yield 76%, mp
d
160.75, 156.28, 154.34, 152.36, 136.44, 135.67, 130.92, 124.37,
225e226 ꢀC. 1H NMR (400 MHz, DMSO-d6):
d 2.10 (m, 2H), 2.15 (s,
122.67, 122.31, 117.97, 113.75, 113.47, 113.28, 112.24, 111.71, 102.34,
19.01, 9.64. Calcd. for C19H14FNO3: C, 59.39; H, 3.67; N, 3.67; Found:
C, 59.20; H, 3.78; N, 3.61%.
3H), 2.72 (m, 2H), 3.06 (m, 2H), 3.07 (s, 3H), 3.24 (s, 3H), 5.95 (d, 1H,
J ¼ 12.0 Hz), 7.77 (s, 1H), 7.94 (d, 1H, J ¼ 12.0 Hz), 15.45 (br s, 1H). 13
C
NMR (100 MHz, DMSO-d6): d 188.12, 164.95, 160.96, 159.48, 155.16,
153.37, 127.34, 125.17, 120.53, 117.52, 110.56, 92.98, 41.19, 31.69,
30.18, 22.95, 12.89, 8.21. Calcd. for C18H19NO4: C, 69.00; H, 6.11; N,
4.47; Found: C, 68.88; H, 6.26; N, 4.41%.
4.2.3. General procedure for the preparation of 6-[3-
(dimethylamino)prop-2-enoyl]-7-hydroxy-8-methylcoumarins
(26e32)
A mixture of 10 mmol coumarin (1e7) and 1.78 g (15 mmol)
DMFDMA in dry toluene (25 ml) was refluxed for 3e6 h (TLC
control). The crystals which were precipitated after concentration
were filtered of, washed with petroleum ether and crystallized
from ethanol.
4.2.3.7. 2-[3-(Dimethylamino)prop-2-enoyl]-3-hydroxy-4-methyl-
7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one (32). Yield 71%, mp
209e210 ꢀC. 1H NMR (300 MHz, DMSO-d6):
d 1.77 (m, 4H), 2.14 (s,
3H), 2.40 (m, 2H), 2.83 (m, 2H), 3.06 (s, 3H), 3.23 (s, 3H), 5.98 (d, 1H,
J ¼ 12.0 Hz), 7.89 (s, 1H), 7.95 (d, 1H, J ¼ 12.0 Hz), 15.60 (br s, 1H). 13
C
NMR (100 MHz, DMSO-d6):
d 187.12, 164.93, 162.42, 159.82, 153.10,
4.2.3.1. 6-[3-(Dimethylamino)prop-2-enoyl]-7-hydroxy-4,8-
148.76, 125.32, 123.61, 120.95, 117.15, 111.73, 93.26, 41.25, 24.96,
24.01, 21.61, 21.29, 12.89, 8.35. Calcd. for C19H21NO4: C, 69.71; H,
6.47; N, 4.28; Found: C, 69.81; H, 6.46; N, 4.31%.
dimethyl-2H-chromen-2-one (26). Yield 88%, mp 211e212 ꢀC. 1H
NMR (400MHz, DMSO-d6):d2.17(s, 3H), 2.47 (s, 3H), 3.09(s, 3H), 3.17
(s, 3H), 6.01 (d, 1H, J ¼ 12.0 Hz), 6.14 (s, 1H), 7.96 (d, 1H, J ¼ 12.0 Hz),
7.98 (s, 1H), 15.20 (br s, 1H). 13C NMR (100 MHz, DMSO-d6): 188.34,
165.64, 161.96, 160.85, 157.52, 154.30, 125.92, 120.41, 117.90, 115.84,
112.20, 92.16, 41.59, 18.63, 12.45, 8.11. Calcd. for C16H17NO4: C, 66.89;
H, 5.96; N, 4.87; Found: C, 66.95; H, 5.81; N, 4.76%.
4.2.4. General procedure for the preparation of 6-(2-
aminopyrimidin-4-yl)-7-hydroxycoumarins (33e39)
A mixture of 2 mmol enaminone (26e32) and 0.73 g (6 mmol)
guanidine carbonate in dry pyridine (10 ml) was refluxed for
6e10 h (TLC control). The reaction mixture was poured onto
crushed ice. The precipitate that formed was filtered of, washed
with water, dried and crystallized from propanol-2.
4.2.3.2. 6-[3-(Dimethylamino)prop-2-enoyl]-4-ethyl-7-hydroxy-8-
methyl-2H-chromen-2-one (27). Yield 76%, mp 202e203 ꢀC. 1H
NMR (400 MHz, DMSO-d6):
d
1.26 (t, 3H, J ¼ 7.2 Hz), 2.15 (s, 3H),
2.90 (q, 2H, J ¼ 7.2 Hz), 3.08 (s, 3H), 3.25 (s, 3H), 6.01 (d, 1H,
4.2.4.1. 6-(2-Aminopyrimidin-4-yl)-7-hydroxy-4,8-dimethyl-2H-
J ¼ 12.0 Hz), 6.11 (s, 1H), 7.98 (d,1H, J ¼ 12.0 Hz), 8.01 (s, 1H), 14.95
chromen-2-one (33). Yield 85%, mp 236e237 ꢀC. 1H NMR (400 MHz,
(br s, 1H). 13C NMR (100 MHz, DMSO-d6):
d
189.48, 164.48, 160.50,
DMSO-d6):
7.42 (d, J ¼ 5.6 Hz, 1H), 8.06 (s, 1H), 8.41 (d, J ¼ 5.6 Hz, 1H), 14.92 (br
s, 1H). 13C NMR (100 MHz, DMSO-d6):
163.45, 161.85, 160.99,
160.30, 158.44, 154.41, 149.97, 121.83, 113.93, 113.02, 111.53, 109.26,
d 2.19 (s, 3H), 2.46 (s, 3H), 6.17 (s, 1H), 7.28 (br s, 2H),
159.02, 156.60, 154.89, 122.92, 116.62, 112.41, 110.73, 108.90, 89.56,
45.62, 38.19, 24.16, 12.40, 8.03. Calcd. for C17H19NO4: C, 67.76; H,
6.36; N, 4.65; Found: C, 67.91; H, 6.41; N, 6.72%.
d