PAPER
Pyrido[3,4-b]pyrazines and Pyrido[2,3-b]pyrazines
805
MS (ESI): m/z (%) = 359 [(M + H), 100].
13C NMR (100 MHz, DMSO-d6): d = 155.5 (C), 155.1 (C), 152.0
(C), 151.7 (C), 147.7 (C), 140.2 (CH), 140.2 (C), 138.6 (C), 138.5
(C), 133.6 (C), 133.4 (C), 130.9 (CH), 130.0 (CH), 129.9 (CH),
129.3 (CH), 128.9 (CH), 128.4 (CH), 128.3 (CH), 123.1 (CH),
118.9 (CH), 118.5 (CH), 117.8 (CH).
Anal. Calcd for C21H18N4O2: C, 70.38; H, 5.06; N, 15.63. Found: C,
70.24; H, 5.05; N, 15.69.
Ureas and Thioureas 23a–f from 22a,b; General Procedure
Method 6: To a soln of 22a,b (0.5 mmol) in DMF (15 mL) was add-
ed portionwise 60% NaH in mineral oil (0.6 mmol). The mixture
was stirred at r.t. for 30 min and then an isocyanate or an isothiocy-
anate (0.5 mmol) was added. The reaction was stirred at r.t. until the
reaction was complete (monitored by TLC). The crude product was
purified by column chromatography (silica gel, CH2Cl2–EtOH,
from 10:0 to 9:1) to give the desired compounds.
MS (ESI): m/z (%) = 404 [(M + H), 100], 406 [(M + H) + 2, 40].
Anal. Calcd for C22H18ClN5O: C, 69.10; H, 4.01; N, 15.50. Found:
C, 69.06; H, 4.02; N, 15.47.
N-[2,3-Bis(4-methoxyphenyl)pyrido[2,3-b]pyrazin-8-yl]-N¢-eth-
ylurea (23d)
Yellow powder; yield: 107 mg (50%, method 7); mp 242–243 °C;
Method 7: To a soln of 22a,b (0.8 mmol) in pyridine (20 mL) was
added an isocyanate or an isothiocyanate (0.8 mmol) and the mix-
ture was heated at reflux until the reaction was complete (monitored
by TLC). Pyridine was removed under reduced pressure and the
crude product was purified by column chromatography (silica gel,
CH2Cl2–EtOH, from 10:0 to 4:1) to yield the desired compounds.
Rf = 0.64 (CH2Cl2–EtOH, 9:1).
IR (KBr): 3215, 1689, 1609, 1561 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 10.12 (br s, 1 H), 9.16 (br s, 1
H), 8.40 (d, J = 9.0 Hz, 1 H), 7.68 (d, J = 9.0 Hz, 1 H), 7.51–7.47
(m, 4 H), 7.00–6.94 (m, 4 H), 3.83 (s, 3 H), 3.82 (s, 3 H) 3.50 (q,
J = 7.3 Hz, 2 H), 1.20 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 160.1 (C), 159.8 (C), 155.4
(C), 154.7 (C), 154.4 (C), 150.6 (C), 147.8 (C), 139.5 (CH), 132.8
(C), 131.4 (CH), 131.2 (CH), 131.1 (C), 131.0 (C), 118.0 (CH),
113.9 (CH), 113.8 (CH), 55.4 (CH3), 55.3 (CH3), 34.2 (CH2), 15.5
(CH3).
N-(2,3-Diphenylpyrido[2,3-b]pyrazin-8-yl)-N¢-ethylurea (23a)
Yellow powder; yield: 151 mg (82%, method 7).
IR (KBr): 3219, 2954, 1674, 1543 cm–1; mp 257–258 °C; Rf = 0.61
(CH2Cl2–EtOH, 9:1).
1H NMR (400 MHz, DMSO-d6): d = 10.19 (br s, 1 H), 9.14 (br s, 1
H), 8.46 (d, J = 9.1 Hz, 1 H), 7.75 (d, J = 9.1 Hz, 1 H), 7.53–7.38
(m, 10 H), 3.40 (m, 2 H), 1.21 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 155.7 (CO), 155.2 (C), 154.3
(C), 148.0 (C), 139.6 (CH), 138.7 (C), 138.6 (C), 133.2 (C), 129.9
(CH), 129.8 (CH), 129.1 (CH), 128.8 (CH), 128.3 (CH), 128.2
(CH), 118.6 (CH), 34.2 (CH2), 15.5 (CH3).
MS (ESI): m/z (%) = 430 [(M + H), 100].
Anal. Calcd for C24H23N5O3: C, 67.12; H, 5.40; N, 16.31. Found: C,
67.02; H, 5.38; N, 16.33.
N-[2,3-Bis(4-methoxyphenyl)pyrido[2,3-b]pyrazin-8-yl]-N¢-
phenylurea (23e)
Yellow powder; yield: 122 mg (51%, method 6); mp 244–245 °C;
Rf = 0.61 (CH2Cl2–EtOH, 9:1).
MS (ESI): m/z (%) = 370 [(M + H), 100].
Anal. Calcd for C22H19N5O: C, 71.53; H, 5.18; N, 18.96. Found: C,
71.42; H, 5.17; N, 19.02.
IR (KBr): 3210, 3045, 1687, 1600, 1559 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.59 (br s, 1 H), 10.42 (br s,
1 H), 8.49 (d, J = 9.2 Hz, 1 H), 7.83 (d, J = 9.2 Hz, 1 H), 7.65–7.39
(m, 8 H), 7.14 (t, J = 7.3 Hz, 1 H), 7.01 (d, J = 8.9 Hz, 2 H), 6.98 (d,
J = 8.9 Hz, 2 H), 3.84 (s, 3 H), 3.82 (s, 3 H).
13C NMR (100 MHz, DMSO-d6): d = 160.2 (CO), 159.8 (C), 155.0
(C), 152.0 (C), 151.1 (C), 147.6 (C), 140.0 (CH), 138.7 (C), 133.0
(C), 131.5 (CH), 131.2 (CH), 131.0 (CH), 129.3 (CH), 123.4 (CH),
119.5 (CH), 118.0 (CH), 114.0 (CH), 113.8 (CH), 55.4 (CH3), 55.30
(CH3).
N-(2,3-Diphenylpyrido[2,3-b]pyrazin-8-yl)-N¢-phenylurea
(23b)
Beige powder; yield: 115 mg (55%, method 6); mp 255–256 °C;
Rf = 0.61 (CH2Cl2–EtOH, 9:1).
IR (KBr): 3234, 3040, 1682, 1600, 1558 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.54 (br s, 1 H), 10.48 (br s,
1 H), 8.55 (d, J = 9.2 Hz, 1 H), 7.89 (d, J = 9.2 Hz, 1 H), 7.72–7.39
(m, 14 H), 7.13 (t, J = 7.4 Hz, 1 H).
13C NMR (100 MHz, DMSO-d6): d = 161.2 (C), 160.0 (C), 151.4
(C), 144.1 (CH), 140.1 (C), 137.2 (CH), 136.9 (CH), 134.6 (C),
132.9 (CH), 132.2 (C), 131.4 (CH), 131.1 (CH), 130.9 (C), 130.7
(C), 130.5 (C), 129.3 (CH), 122.5 (CH), 118.1 (CH), 117.3 (CH),
117.2 (CH).
MS (ESI): m/z (%) = 478 [(M + H), 100].
Anal. Calcd for C28H23N5O3: C, 70.43; H, 4.85; N, 14.67. Found: C,
70.19; H, 4.88; N, 14.73.
N-(2,3-Diphenylpyrido[2,3-b]pyrazin-8-yl)-N¢-ethylthiourea
(23f)
Yellow powder; yield: 169 mg (55%, method 7); mp 233–234 °C;
Rf = 0.77 (CH2Cl2–EtOH, 9:1).
MS (ESI): m/z (%) = 418 [(M + H), 100].
Anal. Calcd for C26H19N5O: C, 74.80; H, 4.59; N, 16.78. Found: C,
74.82; H, 4.58; N, 16.79.
IR (KBr): 3412, 3194, 1566, 1524, 1232 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 12.23 (br s, 1 H), 11.31 (br s,
1 H), 8.54 (d, J = 8.9 Hz, 1 H), 7.72 (d, J = 8.9 Hz, 1 H), 7.74–7.30
(m, 10 H), 3.77 (m, 2 H), 1.32 (t, J = 7.3 Hz, 3 H).
N-(3-Chlorophenyl)-N¢-(2,3-diphenylpyrido[2,3-b]pyrazin-8-
yl)urea (23c)
Beige powder; yield: 120 mg (53%, method 6); mp 243–244 °C;
13C NMR (100 MHz, DMSO-d6): d = 179.7 (C), 155.6 (C), 155.3
(C), 151.8 (C), 147.2 (C), 140.3 (CH), 138.6 (C), 133.4 (C), 130.0
(CH), 129.9 (CH), 129.3 (CH), 129.0 (CH), 128.4 (CH), 128.3
(CH), 119.2 (CH), 55.2 (CH2), 14.1 (CH3).
Rf = 0.64 (CH2Cl2–EtOH, 9:1).
IR (KBr): 3222, 1692, 1595, 1549 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 11.63 (br s, 1 H), 10.55 (br s,
1 H), 8.56 (d, J = 9.2 Hz, 1 H), 7.99–7.89 (m, 3 H), 7.57–7.17 (m,
12 H).
MS (ESI): m/z (%) = 386 [(M + H), 100].
Anal. Calcd for C22H19N5S: C, 68.55; H, 4.97; N, 18.17. Found: C,
68.54; H, 4.96; N, 18.19.
Synthesis 2011, No. 5, 794–806 © Thieme Stuttgart · New York