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M. L. Read et al. / Bioorg. Med. Chem. 18 (2010) 3885–3897
(C-4); MS EI m/z (rel. %): 281 (100, M+), 280 (18), 266 (17), 250 (4),
146 (6), 136 (53), 121 (59); HRMS: found 281.1164, calcd for
C16H15N3O2 281.1164.
in furyl C-2), 147.6 (C-5 in furyl or C-2), 153.1 (C-2 in furyl),
158.2 (C-4 in Ar or C-4), 158.7 (C-4 in Ar or C-4); MS EI m/z (rel.
%): 310 (41, M+), 295 (10), 281 (10), 189 (9). 150 (8), 121 (100),
106 5), 78 (8), 77 (6); HRMS: found 310.1422, calcd for
C17H18N4O2 310.1430; Anal. Calcd for C17H18N4O2: C, 65.79; H,
5.85; N, 18.05. Found: C, 66.13; H, 5.97; N, 17.68.
4.15.2. 6-(2-Furyl)-N-(4-methoxybenzyl)-N-methylpyrimidine-
4-amine (3b)
EtOAc–hexane (1:3) followed by EtOAc–hexane (1:2) were used
as eluents for flash chromatography; yield 99 mg (67%), colorless
oil. 1H NMR (CDCl3, 200 MHz) d 3.10 (br s, 3H, NCH3), 3.60 (s, 3H,
OCH3), 4.82 (br s, 2H, CH2), 6.55 (dd, J = 3.4 and 1.8 Hz, 1H, H-4 in
furyl), 6.83–6.90 (m, 3H, Ar and H-5), 7.16–7.20 (m, 3H, Ar and H-
3 in furyl), 7.53 (br s, 1H, H-5 in furyl), 8.63 (s, 1H, H-2); 13C NMR
(CDCl3, 50 MHz) d 35.2 (NCH3), 51.8 (CH2), 55.3 (OCH3), 95.5 (C-
5), 110.9 (CH in furyl), 112.2 (CH in furyl), 114.1 (CH in Ar), 128.4
(CH in Ar), 129.0 (C-1 in Ar), 143.9 (CH in furyl), 152.3 (C-2 in furyl
or C-6), 153.7 (C-2 in furyl or C-6), 158.0 (C-2), 158.9 (C-4 in Ar),
162. 3 (C-4); MS EI m/z (rel. %): 295 (97, M+), 280 (100), 174 (23),
150 (18), 148 (9), 121 (70), 118 (13); HRMS: found 295.1317, calcd
for C17H17N3O2 295.1321; Anal. Calcd for C17H17N3O2: C, 69.14; H,
5.80; N, 14.23. Found: C, 69.27; H, 5.94; N, 13.80.
4.15.6. 4-(2-Furyl)-6-(4-methoxybenzyloxy)pyrimidine-5-amine
(3i)
EtOAc–hexane (1:3) was used as eluent for flash chromatogra-
phy and the reaction was performed in 1.37 mmol scale; yield
247 mg (61%), mp 114–116 °C, yellow crystals. 1H NMR (CDCl3,
200 MHz) d 3.80 (s, 3H, OCH3), 4.73 (br s, 2H, NH2), 5.40 (s, 2H,
CH2), 6.57 (m, 1H, H-4 in furyl), 6.91 (d, J = 8.4 Hz, 2H, Ar), 7.15
(m 1H, H-3 in furyl), 7.39 (d, J = 8.4 Hz, 2H, Ar), 7.57 (br s, 1H, H-
5 in furyl), 8.22 (s, 1H, H-2); 13C NMR (CDCl3, 50 MHz) d 55.2
(CH3), 68.3 (CH2), 110.3 (CH in furyl), 111.8 (CH in furyl), 113.9
(CH in Ar), 124.4 (C-5), 128.2 (C-1 in Ar), 130.0 (CH in Ar), 135.1
(C-2 in furyl or C-4), 142.8 (C-5 in furyl or C-2), 146.0 (C-5 in furyl
or C-2), 153.4 (C-2 in furyl or C-4), 158.6 (C-4 in Ar or C-6), 159.7
(C-4 in Ar or C-6); MS EI m/z (rel. %): 297 (46, M+), 177 (3), 149 (2),
148 (2), 122 (17), 121 (100), 78 (7), 77 (6); HRMS: found 297.1115,
calcd for C16H15N3O3 297.1113.
4.15.3. 4-(2-Furyl)-6-(4-methoxybenzyloxy)pyrimidine (3c)
EtOAc–hexane (1:4) was used for flash chromatography and the
reaction was performed in 0.54 mmol scale; yield 140 mg (92%),
mp 108–109 °C, colorless crystals. 1H NMR (CDCl3, 200 MHz) d
3.80 (s, 3H, CH3), 5.38 (s, 2H, CH2), 6.53 (m, 1H, H-4 in furyl),
6.90 (d, J = 8.6 Hz, 2H, Ar), 7.02 (s, 1H, H-5), 7.17 (br d, J = 3.4 Hz,
H-3 in furyl), 7.38 (d, J = 8.6 Hz, 2H, Ar), 7.54 (br s, 1H, H-5 in furyl),
8.73 (s, 1H, H-2); 13C NMR (CDCl3, 50 MHz) d 55.3 (OCH3), 68.0
(CH2), 101.4 (C-5), 111.6 (CH in furyl), 112.2 (CH in furyl), 113.9
(CH in Ar), 128.1 (C-1 in Ar), 129.9 (CH in Ar), 144.6 (CH in furyl),
151.6 (C-2 in furyl), 155.9 (C-4), 158.2 (C-2), 159.5 (C-4 in Ar),
169.7 (C-6); MS EI m/z (rel. %): 282 (67, M+), 253 (7), 147 (13),
146 (37), 137 (7), 122 (12), 121 (100); HRMS: found 282.1006,
calcd for C16H14N2O3 282.1004.
4.15.7. 6-(2-Furyl)-N-(4-methoxybenzyl)-5-nitropyrimidine-4-
amine (3m)
EtOAc–hexane (3:7) was used as eluent for flash chromatogra-
phy; yield 104 mg (63%), mp 118.5–119.0 °C, yellow crystals. 1H
NMR (DMSO-d6, 300 MHz) d 3.70 (s, 3H, CH3), 4.56 (d, J = 5.8 Hz,
2H, CH2), 6.73 (dd, J = 3.5 and 1.7 Hz, 1H, H-4 in furyl), 6.87 (d,
J = 8.7 Hz, 2H, Ar), 7.24 (d, J = 8.7 Hz, 2H, Ar), 7.32 (dd, J = 3.5 and
0.8 Hz, 1H, H-3 in furyl), 7.95 (dd, J = 1.7 and 0.8 Hz, 1H, H-5 in fur-
yl), 8.49 (t, J = 5.8 Hz, 1H, NH), 8.52 (s, 1H, H-2); 13C NMR (DMSO-
d6, 75 MHz) d 43.2 (CH2), 55.0 (CH3), 112.7 (C-4 in furyl), 113.7 (CH
in Ar), 115.7 (C-3 in furyl), 126.4 (C-5), 128.6 (CH in Ar), 130.6 (C-1
in Ar), 143.9 (C-6), 147.3 (C-5 in furyl), 148.1 (C-2 in furyl), 153.3
(C-4), 158.2 (C-2), 158.3 (C-4 in Ar); MS EI m/z (rel. %): 326 (11,
M+), 309 (100), 278 (96), 250 (22), 190 (42), 121 (78); HRMS: found
326.1014, calcd for C16H14N4O4 326.1015; Anal. Calcd for
C16H14N4O4: C, 58.89; H, 4.32; N, 17.17. Found: C, 58.96; H, 4.35;
N, 17.05. An alternative procedure for the synthesis of 3m starting
from 4f is given below.
4.15.4. 6-(2-Furyl)-N4-(4-methoxybenzyl)pyrimidine-4,5-
diamine (3g)
EtOAc–hexane (1:5) followed by EtOAc–hexane (1:2) and
EtOAc–hexane (1:1) were used as eluents for flash chromatography
and the reaction was performed on 0.63 mmol scale; yield 84 mg
(45%), mp 157–159 °C, off-white powdery crystals. 1H NMR (CDCl3,
200 MHz) d 3.79 (s, 3H, OCH3), 4.04 (br s, 2H, NH2), 4.61 (d,
J = 5.0 Hz, 2H, CH2), 5.04 (br s, 1H, NH), 6.56 (m, 1H, H-4 in furyl),
6.87 (d, J = 8.2 Hz, 2H, Ar), 7.13 (br d, J = 3.4 Hz, 1H, H-3 in furyl),
7.29 (d, J = 8.2 Hz, 2H, Ar), 7.56 (br s, 1H, H-5 in furyl), 8.31 (s, 1H,
H-2); 13C NMR (CDCl3, 50 MHz) d 45.0 (CH2), 55.2 (OCH3), 110.7
(CH in furyl), 111.8 (CH in furyl), 113.9 (CH in Ar), 121.1 (C-5),
129.2 (CH in Ar), 130.4 (C-1 in Ar), 135.5 (C-6), 142.6 (C-5 in furyl
or C-2), 149.6 (C-5 in furyl or C-2), 153.5 (C-2 in furyl or C-4),
155.4 (C-2 in furyl or C-4), 158.9 (C-4 in Ar); MS EI m/z (rel. %):
296 (36, M+), 278 (1), 264 (1), 187 (1), 148 (29), 136 (4), 122 (9),
121 (100); HRMS: found 296.1264, calcd for C16H16N4O2 296.1273.
4.15.8. 6-(2-Furyl)-N-(4-methoxybenzyl)-N-methyl-5-
nitropyrimidine-4-amine (3n)
Hexane followed by EtOAc–hexane (1:1) were used as eluents
for flash chromatography and the reaction was run in 0.43 mmol
scale; yield 104 mg (63%), mp 79–81 °C, yellow crystals. 1H NMR
(CDCl3, 300 MHz) d 2.94 (s, 3H, NCH3), 3.78 (s, 3H, OCH3), 4.86 (s,
2H, CH2), 6.53 (dd, J = 3.6 and 1.7 Hz, 1H, H-4 in furyl), 6.86 (d,
J = 8.7 Hz, 2H, Ar), 7.18 (d, J = 8.7 Hz, 2H, Ar), 7.26 (dd, J = 3.6 and
0.7 Hz, 1H, H-3 in furyl), 7.56 (dd, J = 1.7 and 0.7 Hz, 1H, H-5 in fur-
yl), 8.55 (s, 1H, H-2); 13C NMR (CDCl3, 75 MHz) d 35.0 (NCH3), 54.3
(CH2), 55.3 (OCH3), 112.3 (C-4 in furyl), 114.2 (CH in Ar), 116.0 (C-3
in furyl), 127.4 (C-5), 128.2 (C-1 in Ar), 128.9 (CH in Ar), 146.0 (C-5
in furyl), 146.6 (C-6), 148.0 (C-2 in furyl), 153.9 (C-4), 156.5 (C-2),
159.2 (C-4 in Ar); MS EI m/z (rel. %): 340 (0.1, M+), 204 (29), 187
(100), 121 (94); HRMS: found 340.1178, calcd for C17H16N4O4
340.1172; Anal. Calcd for C17H16N4O4: C, 59.99; H, 4.74; N, 16.43.
Found: C, 59.92; H, 4.79; N, 16.43.
4.15.5. 6-(2-Furyl)-N4-(4-methoxybenzyl)-N4-
methylpyrimidine-4,5-diamine (3h)
EtOAc–hexane (1:1) was used as eluent for flash chromatogra-
phy and the reaction was performed on 1.00 mmol scale; yield
288 mg (93%), yellow oil. 1H NMR (CDCl3, 200 MHz) d 2.83 (br s,
3H, NCH3), 3.78 (s, 3H, OCH3), 4.39 (s, 2H, CH2), 4.53 (br s, 2H,
NH2), 6.57 (dd J = 3.4 and 1.8 Hz, 1H, H-4 in furyl), 6.86 (d,
J = 8.8 Hz, 2H, Ar), 7.16 (br d, J = 1.8 Hz, 1H, H-3 in furyl), 7.22 (d,
J = 8.8 Hz, 2H, Ar), 7.57 (br s, 1H, H-5 in furyl), 8.34 (s, 1H, H-2);
13C NMR (CDCl3, 50 MHz) d 37.4 (NCH3), 54.8 (CH2), 55.2 (OCH3),
111.1 (CH in furyl), 111.9 (CH in furyl), 113.9 (CH in Ar), 127.2
(C-5), 128.8 (CH in Ar), 129.6 (C-1 in Ar), 136.8 (C-6), 142.9 (C-5
4.16. 2-Chloro-6-(2-furyl)-N-(4-methoxybenzyl)pyrimidine-4-
amine (3d)
A mixture of 2,4-dichloro-6-(2-furyl)pyrimidine 4a (320 mg,
1.50 mmol), 4-methoxybenzylamine (200 mg, 1.50 mmol) and