NJC
Paper
3477 (CONH stretching), 3195 (N–H stretching), 2859 87%; m.p. 261–263 1C; IR (ATR, n cmꢀ1): 3289 (CONH stretching),
(C–H stretching), 1718, 1683, 1609 (CQO stretching), 1465, 3267 (N–H stretching), 2854 (C–H stretching), 1753, 1632 (CQO
1
1228, 1022, 826, 785. H NMR (400 MHz, DMSO-d6, ppm): 10.08 stretching), 1587, 1459, 1234, 853, 779. 1H NMR (400 MHz,
(s, br. 2H, NH), 7.12–7.29 (m, 4H, Ar-H), 5.99 (s, 2H, NH) 4.86 (s, DMSO-d6, ppm): 11.36 (s, 2H, NH), 11.21 (s, 2H, NH), 10.23
1H, pyrimidine), 3.75 (s, 3H, OCH3). 13C NMR (100 MHz, DMSO-d6, (s, 1H, NH), 7.23–7.45 (m, 2H, Ar-H), 7.09–7.19 (m, 2H, Ar-H),
ppm): 169.92 (2C), 163.38 (2C), 157.28, 154.56 (2C), 146.49, 138.31, 5.12 (s, 1H, pyrimidine). 13C NMR (100 MHz, DMSO-d6, ppm):
130.73 (2C), 118.51 (2C), 87.45, 59.16, 41.32. Mass (LCMS): m/z 356 168.96, 159.34, 153.37, 152.32, 144.67, 134.23, 128.75, 127.32,
[M + H]+. Anal. calcd for C16H13N5O5: N: 19.71, C: 54.09, H: 3.69; 125.89, 122.43, 121.67, 116.32, 115.76, 88.12, 37.40.
found: N: 19.67; C: 54.14; H: 3.67%.
5-(2-Nitro phenyl)-1,3,5,7,9,10-hexahydropyrimido[50,40-5,6]-
5-(4-Methylphenyl)-1,3,5,7,9,10-hexahydropyrimido[50,40-5,6]- pyridine[2,3-d]pyrimidine-2,4,6,8-tetraone (3h). White solid,
pyridine[2,3-d]pyrimidine-2,4,6,8-tetraone (3c). White solid, yield 88%; m.p. 256–258 1C; IR (ATR, n cmꢀ1): 3343 (CONH
yield 89%; m.p. 290–292 1C; IR (ATR, n cmꢀ1): 3560 (CONH stretching), 3421 (CONH stretching), 3183 (N–H stretching),
stretching), 3469 (CONH stretching), 3187 (N–H stretching), 2870 (C–H stretching), 1743, 1662, 1629 (CQO stretching),
2843 (C–H stretching), 1705, 1675, 1623 (CQO stretching), 1470, 1237, 870, 795. 1H NMR (400 MHz, DMSO-d6, ppm):
1463, 1230, 1063, 824, 781. 1H NMR (400 MHz, DMSO-d6, 11.39 (s, 2H, NH), 11.27 (s, 2H, NH), 10.48 (s, 1H, NH), 7.11–
ppm): 10.12 (s, br. 2H, NH), 7.09–7.25 (m, 4H, Ar-H), 5.98 7.25 (m, 4H, Ar-H), 5.08 (s, 1H, pyrimidine). 13C NMR (100 MHz,
(s, 2H, NH), 4.89 (s, 1H, pyrimidine), 2.46 (s, 3H, OCH3). DMSO-d6, ppm): 168.96, 162.39, 158.82, 152.76, 143.32, 129.31,
13C NMR (100 MHz, DMSO-d6, ppm): 169.57 (2C), 162.98 (2C), 128.64, 127.90, 125.32, 122.12, 121.67, 116.96, 115.42, 84.21, 37.46.
157.24, 154.57 (2C), 139.51, 138.75, 130.23 (2C), 124.13 (2C),
5-(4-(Dimethylamino)phenyl)-9,10-dihydropyrido[2,3-d:6,5-d0]-
87.78, 41.32, 37.38. Mass (LCMS): m/z 340 [M + H]+. Anal. calcd dipyrimidine-2,4,6,8(1H,3H,5H,7H)-tetraone (3i). Orange solid,
for C16H13N5O4: N: 20.64, C: 56.64; H: 3.86; found: N: 20.67; yield 90%; m.p. 286–288 1C; IR (ATR, n cmꢀ1): 3414 (CONH
C: 55.87; H: 3.85%.
stretching), 3160 (N–H stretching), 2817 (C–H stretching), 1657
5-(4-Chlorophenyl)-1,3,5,7,9,10-hexahydropyrimido[50,40-5,6]- (CQO stretching), 1458, 1243, 854, 791. 1H NMR (400 MHz,
pyridine[2,3-d]pyrimidine-2,4,6,8-tetraone (3d). White solid, yield CDCl3, ppm): 11.51 (s, 2H, NH), 11.29 (s, 2H, NH), 10.51 (s, 1H,
92%; m.p. 4 300 1C; IR (ATR, n cmꢀ1): 3572 (CONH stretching), NH), 7.61–7.82 (m, 2H, Ar-H), 7.12–7.42 (m, 2H, Ar-H), 5.06 (s,
3468 (CONH stretching), 3178 (N–H stretching), 2851 (C–H stretch- 1H, pyrimidine), 2.45 (s, 6H, CH3). 13C NMR (100 MHz, DMSO-d6,
ing), 1709, 1672, 1630 (CQO stretching), 1465, 1238, 1071, 822, ppm): 162.74 (2C), 158.85 (2C), 142.23, 136.06 (2C), 129.30,
780. 1H NMR (400 MHz, DMSO-d6, ppm): 11.39 (s, 2H, NH), 11.32 127.49, 120.19 (2C), 111.28 (2C), 85.87, 50.40, 35.59. Mass
(s, 2H, NH), 10.37 (s, 1H, NH) 7.12–7.33 (m, 4H, Ar-H), 5.04 (s, 1H, (LCMS): m/z 369 [M + H]+. Anal. calcd for C17H16N6O4: N: 22.82;
pyrimidine). 13C NMR (100 MHz, DMSO-d6, ppm): 169.23 (2C), C: 55.43; H: 4.38; found: N: 22.88; C: 55.46; H: 4.40%.
162.76 (2C), 157.29, 154.55 (2C), 138.49, 137.68, 131.65 (2C), 123.27
(2C), 88.35, 37.21.
5-(3,4-Dimethoxyphenyl)-9,10-dihydropyrido[2,3-d:6,5-d0]dipyr-
imidine-2,4,6,8(1H,3H,5H,7H)-tetraone (3j). Pale yellow solid,
5-(3-Chlorophenyl)-1,3,5,7,9,10-hexahydropyrimido[50,40-5,6]- yield 89%; m.p. 294–296 1C; IR (ATR, n cmꢀ1): 3325 (CONH
pyridine[2,3-d]pyrimidine-2,4,6,8-tetraone (3e). White solid, yield stretching), 3145 (N–H stretching), 2865 (C–H stretching), 1720,
91%; m.p. 4 300 1C; IR (ATR, n cmꢀ1): 3571 (CONH stretching), 1689 (CQO stretching), 1426, 1267, 880, 787. 1H NMR (400 MHz,
3469 (CONH stretching), 3180 (N–H stretching), 2853 (C–H stretch- DMSO-d6, ppm): 11.39 (s, 2H, NH), 11.24 (s, 2H, NH), 10.34 (s, 1H,
ing), 1711, 1673, 1629 (CQO stretching), 1467, 1240, 825, 787. NH), 7.09–7.78 (m, 3H, Ar-H), 5.13 (s, 1H, pyrimidine), 3.57 (s, 6H,
1H NMR (400 MHz, DMSO-d6, ppm): 11.30 (s, 2H, NH), 11.28 (s, OCH3), 2.33 (s, 3H, CH3). 13C NMR (100 MHz, DMSO-d6, ppm):
2H, NH), 10.35 (s, 1H, NH), 7.09–7.19 (m, 4H, Ar-H), 5.06 (s, 1H, 167.45 (2C), 159.48 (2C), 142.76, 136.64 (2C), 129.27, 127.68,
pyrimidine). 13C NMR (100 MHz, DMSO-d6, ppm): 169.29 (2C), 121.89, 120.65, 118.49 (2C), 85.59, 55.87, 37.13.
161.89 (2C), 156.54, 154.52 (2C), 138.47, 137.89, 133.45 (2C), 122.78
(2C), 88.37, 37.22.
5-Butyl-9,10-dihydropyrido[2,3-d:6,5-d0]dipyrimidine-2,4,6,8-
(1H,3H,5H,7H)-tetraone (3k). Yellow solid, yield 87%; m.p. 232–
5-(4-Hydroxyphenyl)-1,3,5,7,9,10-hexahydropyrimido[50,40-5,6]- 234 1C; IR (ATR, n cmꢀ1): 3176 (CONH stretching), 2870 (C–H
pyridine[2,3-d]pyrimidine-2,4,6,8-tetraone (3f). Yellow solid, yield stretching), 1767, 1659 (CQO stretching), 1489, 1245, 838, 723.
95%; m.p. 4 300 1C; IR (ATR, n cmꢀ1): 3270 (CONH stretching), 1H NMR (400 MHz, DMSO-d6, ppm): 11.32 (s, 2H, NH), 11.29 (s,
3190 (N–H stretching), 2812 (C–H stretching), 1727, 1667 (CQO 2H, NH), 10.17 (s, 1H, NH), 3.67 (t, 1H, J = 7.1 Hz, pyrimidine),
stretching), 1535, 1444, 1284, 885, 786. 1H NMR (400 MHz, CDCl3, 1.58–1.48 (m, 2H, CH2), 1.27–1.23 (m, 2H, CH2), 1.18–1.12 (m,
ppm): 11.49 (s, 2H, NH), 11.25 (s, 2H, NH), 10.18 (s, 1H, NH), 2H, CH2), 0.89 (t, 3H, J = 7.2 Hz, CH3). 13C NMR (100 MHz,
7.21–7.40 (m, 2H, Ar-H), 7.18–7.20 (m, 2H, Ar-H), 5.18 (s, 1H, DMSO-d6 ppm): 168.76 (2C), 162.82 (2C), 154.50 (2C), 87.35,
pyrimidine). 13C NMR (100 MHz, DMSO-d6, ppm): 159.96, 158.39, 36.45, 31.17, 25.35, 18.04, 14.25.
153.82, 152.53, 143.74, 128.94, 128.04, 127.54, 125.08, 122.89,
General procedure for the synthesis of pyrimido-(4,5-d)pyrimidine
119.67, 116.96, 113.35, 82.38, 37.37. Mass (LCMS): m/z 342
[M + H]+. Anal. calcd for C15H11N5O5: N: 20.52; C: 52.79; H:
(4a–g)
3.25; found: N: 20.58; C: 52.80; H: 3.22%.
A mixture of substituted aldehydes (1a–k) (1 mmol), barbituric
5-(2-Hydroxyphenyl)-1,3,5,7,9,10-hexahydropyrimido[50,40-5,6]- acid (2a) (2 mmol) and urea (2 mmol) was added to DIPEAc
pyridine[2,3-d]pyrimidine-2,4,6,8-tetraone (3g). Yellow solid, yield (5 mL). The resulting mixture was stirred at room temperature.
This journal is ©The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018 New J. Chem., 2018, 42, 18621--18632 | 18623