Taylor and Liu
151.3, 146.1, 131.4, 128.2, 127.5, 118.1, 113.2, 98.75, 51.9, 34.8,
31.45, 30.5, 26.0, 25.7; FABMS m/z 442 (MH+), 396, 309, 295,
275, 155, 135, 119; HRFABMS calcd for C21H24N5O6 (MH+)
442.1648, found 442.1723. Anal. Calcd for C21H23N5O6: C,
57.14; H, 5.25; N, 15.86. Found: C, 56.94; H, 5.31; N, 15.48.
243, 218, 192, 183, 164, 151, 136, 126, 101, 89, 75, 68; MS
(MH+) 310; HRMS calcd for C12H12ClN5O3 309.0628, found
309.0610.
2,4,6-Tr ia m in o-5-[2-n itr o-1-(2-ch lor op h en yl)eth yl]p yr -
im id in e (21k ): isolated in 89% yield as a light yellow solid:
153 °C dec; IR (KBr) 3636, 3502, 3398, 3351, 1619, 1569, 1433,
1378, 1069, 862, 766, 706 cm-1; 1H NMR (DMSO-d6) δ 7.60 (1
H, d, J ) 7.5 Hz), 7.42 (1 H, d, J ) 7.5 Hz), 7.32 (2 H, q, J )
6.5 Hz), 5.52-5.43 (1 H, m), 5.36 (6 H, br s), 5.31-4.80 (2 H,
m); 13C NMR (CD3COOD) δ 159.3, 154.8, 135.8, 135.6, 132.5,
130.7, 128.9, 127.7, 82.4, 73.75, 37.1; EIMS m/z 308 (M+), 262,
248, 224, 212, 195, 183, 168, 140, 125, 118, 101, 89, 75, 67;
MS (MH+) 309; HRMS calcd for C12H13ClN6O2 308.0788, found
308.0792.
N-[4-(2-Am in o-4-oxo-4,7-d ih yd r o-3H-p yr r olo[2,3-d ]p yr -
im id in -5-yl)ben zoyl]-L-glu ta m ic a cid (n on br id ged a n a -
logu e of Alim ta , 1b): To a mixture of 110 mg (0.247 mmol)
of 25c in 2.0 mL of THF at room temperature was added 1
mL of 1 N NaOH. The mixture changed to deep blue im-
mediately, and was stirred for 3 h. Acetic acid (0.11 mL, 2.0
mmol) was added. The mixture was evaporated to dryness and
3 mL of methanol was added. The solid was collected by
filtration, washed with ethyl acetate, and dried under vacuum
to give 90 mg (80% yield) of 1b as a light blue solid (Note: 1b
is soluble in water): mp 176 °C dec; IR (KBr) 3375, 3204, 2955,
1639, 1600, 1514, 1403, 1298, 1007, 959, 862, 823, 766, 679
2, 6-Dia m in o-5-[2-n it r o-1-(3-ch lor op h en yl)et h yl]-3 H -
p yr im id in -4-on e (21l): isolated in 86% yield as a light yellow
solid: 180 °C dec; IR (KBr) 3489, 3402, 3168, 2910, 1630, 1594,
1
1540, 1493, 1446, 1377, 1174, 1082, 1001, 785, 679 cm-1; H
cm-1 1H NMR (DMSO-d6/D2O) δ 7.97 (2 H, d, J ) 8.0 Hz),
;
NMR (DMSO-d6) δ 9.89 (1 H, s), 7.59 (1 H, s), 7.50 (1 H, d, J
) 7.5 Hz), 7.29 (1 H, t, J ) 7.5 Hz), 7.24 (1 H, d, J ) 8.0 Hz),
6.24 (2 H, br s), 6.13 (2 H, br s), 5.42 (1 H, dd, J ) 12.5 and
7.5 Hz), 5.35 (1 H, dd, J ) 12.5 and 7.5 Hz), 4.36 (1 H, t, J )
7.5 Hz); 13C NMR ((DMSO-d6) δ 162.3, 162.2, 153.7, 143.9,
132.6, 129.8, 127.6, 126.5, 126.4, 85.5, 77.4, 39.0; EIMS m/z
309 (M+), 291, 274, 262, 260, 238, 225, 208, 192, 183, 151, 126,
113, 101, 86, 75, 68; HRMS calcd for C12H12ClN5O3 309.0628,
found 309.0622.
7.76 (2 H, d, J ) 8.0 Hz), 7.09 (1 H, s), 4.13 (1 H, m), 2.04-
1.95 (3 H, m), 1.86 (1 H, m); 13C NMR (DMSO-d6/D2O) δ 178.5,
176.05, 166.4, 160.0, 153.25, 153.15, 138.1, 131.8, 127.6, 127.5,
119.4, 117.0, 97.55, 55.5, 34.3, 29.5; FABMS m/z 399 (M+);
FABHRMS calcd for 399.1179, found 399.1164.
2,6-Dia m in o-5-(2-n it r o-1-p h en et h yl)-3H -p yr im id in -4-
on e (21f): isolated in 92% yield as a light solid: mp 146 °C
dec; IR (KBr) 3379, 3187, 2912, 1622, 1546, 1494, 1436, 1376,
1253, 793, 773 cm-1; 1H NMR (DMSO-d6) δ 9.90 (1 H, s), 7.50
(2 H, d, J ) 8.0 Hz), 7.25 (2 H, t, J ) 7.5 Hz), 7.17 (1 H, t, J
) 7.5 Hz), 6.12 (4 H, s), 5.46 (1 H, dd, J ) 13.0 and 7.5 Hz),
5.30 (1 H, dd, J ) 13.0 and 7.5 Hz), 4.56 (1 H, t, J ) 7.5 Hz);
13C NMR (DMSO-d6) δ 162.3, 153.8, 141.5, 128.0, 127.8, 126.4,
118.65, 86.2, 78.0, 39.35; MS 276 (MH+); EIMS m/z 228 (M+
- HNO2), 180, 149, 126, 102, 91, 77.
2,4,6-Tr ia m in o-5-[2-n itr o-1-(3-ch lor op h en yl)eth yl]p yr -
im id in e (21m ): isolated in 81% yield as a light yellow solid:
182 °C dec; IR (KBr) 3498, 3482, 3381, 3199, 1639, 1608, 1561,
1
1473, 1438, 1382, 804, 682 cm-1; H NMR (DMSO-d6) δ 7.37
(1 H, t, J ) 8.0 Hz), 7.30 (2 H, d, J ) 8.5 Hz), 7.24 (1 H, d, J
) 8.0 Hz), 5.54 (4 H, br s), 5.51 (1 H, dd, J ) 13.5 and 5.0 Hz),
5.44 (2 H, br s), 5.18 (1 H, dd, J ) 13.5 and 9.0 Hz), 5.04 (1 H,
t, J ) 7.5 Hz); 13C NMR (DMSO-d6) δ 162.35, 161.4, 141.85,
133.7, 130.15, 127.0, 126.55, 125.7, 83.6, 75.4, 37.2; MS m/z
308 (M+), 262, 258, 248, 231, 206, 183, 140, 125, 113, 102, 89,
75, 67; HRMS calcd for C12H13ClN6O2 308.0788, found 308.0776.
2, 6-Dia m in o-5-[2-n it r o-1-(4-ch lor op h en yl)et h yl]-3 H -
p yr im id in -4-on e (21n ): isolated in 80% yield as a light yellow
solid: mp 92 °C dec; IR (KBr) 3480, 3390, 3196, 2916, 1624,
1547, 1490, 1436, 1376, 1256, 1093, 1015, 793 cm-1; 1H NMR
(DMSO-d6) δ 9.98 (1 H, s), 7.53 (2 H, d, J ) 7.5 Hz), 7.30 (2 H,
d, J ) 7.5 Hz), 6.21 (2 H, br s), 6.13 (2 H, br s), 5.41 (1 H, t, J
) 7.5 Hz), 5.32 (1 H, t, J ) 7.5 Hz), 4.56 (1 H, t, J ) 7.5 Hz);
13C NMR (DMSO-d6) δ 162.3, 162.2, 153.7, 140.4, 131.0, 129.7,
127.9, 85.75, 77.5, 38.7; EIMS m/z 309 (M+), 291, 274, 262,
249, 233, 206, 192, 183, 151, 142, 126, 102, 89, 75, 68; HRMS
calcd for C12H12ClN5O3 309.0639, found 309.0642.
2,4,6-Tr iam in o-5-(2-n itr o-1-ph en eth yl)pyr im idin e (21g):
isolated in 90% yield as a light yellow solid: mp 127 °C dec;
IR (KBr) 3460, 3342, 3192, 1635, 1554, 1496, 1447, 1377, 1339,
1
1253, 1044, 700, 651 cm-1; H NMR (DMSO-d6) δ 7.34-7.29
(2 H, m), 7.27-7.22 (3 H, m), 5.46 (1 H, dd, J ) 13.0 and 6.5
Hz), 5.16 (1 H, dd, J ) 13.0 and 9.0 Hz), 5.05 (1 H, dd, J )
13.0 and 6.5 Hz); 13C NMR (DMSO-d6) δ163.2, 161.8, 140.3,
129.65, 128.0, 127.8, 85.5, 76.59, 38.4; MS 275 (MH+).
2,6-Diam in o-5-[2-n itr o-1-(3,4,5-tr im eth oxyph en yl)eth yl]-
3H-p yr im id in -4-on e (21h ): isolated in 84% yield as a light
yellow solid: mp 208 °C dec; 1H NMR (DMSO-d6) δ 9.94 (1 H,
s), 6.99 (2 H, s), 6.14 (2 H, br s), 6.12 (2 H, br s), 5.51 (1 H, dd,
J ) 12.5 and 8.0 Hz), 5.24 (1 H, dd, J ) 12.5 and 8.0 Hz), 4.43
(1 H, t, J ) 8.0 Hz), 3.71 (6 H, s), 3.61 (3 H, s); 13C NMR
(DMSO-d6) δ 162.4, 162.3, 153.6, 153.0, 137.2, 136.2, 135.6,
86.1, 77.9, 59.9, 55.8, 39.7; EIMS m/z 318 (M+ - HNO2); 306,
287, 217, 177, 152, 126, 98, 67; HRMS calcd for C15H18N4O4
(M+ - HNO2) 318.1328, found 318.1324.
2,4,6-Tr ia m in o-5-[2-n it r o-1-(3,4,5-t r im et h oxyp h en yl)-
eth yl]p yr im id in e (21i): isolated in 75% yield as a light yellow
solid: mp 176 dec; IR (KBr) 3475, 3377, 3188, 2942, 1614,
1569, 1508, 1447, 1376, 1331, 1241, 1126, 999, 909, 794, 733
cm-1; 1H NMR (DMSO-d6) δ 6.56 (2 H, s), 5.51 (4 H, s), 5.47 (2
H, s), 5.46 (1 H, m), 5.16 (1 H, m), 4.96 (1 H, m), 3.73 (6 H, s),
3.63 (3 H, s); 13C NMR (DMSO-d6) δ 163.4, 162.05, 154.0, 137.4,
135.8, 105.8, 85.2, 76.9, 61.1, 57.1, 38.9; EIMS m/z 364 (M+),
318, 239, 207, 192, 177, 149, 125, 98, 84, 67; HRMS calcd for
2,4,6-Tr ia m in o-5-[2-n itr o-1-(4-ch lor op h en yl)eth yl]p yr -
im id in e (21o): isolated in 87% yield as a light yellow solid:
mp 80 °C dec; IR (KBr) 3476, 3372, 3188, 1617, 1568, 1444,
1375, 1235, 1092, 1014, 802 cm-1; 1H NMR (DMSO-d6) δ 7.40
(2 H, d, J ) 7.5 Hz), 7.29 (2 H, d, J ) 7.5 Hz), 5.60 (4 H, br s),
5.50 (2 H, br s), 5.47 (1 H, m), 5.17 (1 H, t, J ) 8.5 Hz), 5.04
(1 H, t, J ) 8.5 Hz);
13C NMR (DMSO-d6) δ 162.3, 161.25,
138.1, 131.2, 128.9, 128.25, 83.75, 75.5, 37.0; EIMS m/z 308
(M+), 262, 248, 231, 217, 206, 189, 183, 168, 150, 140, 125,
113, 101, 84, 75, 67; HRMS calcd for C12H13ClN6O2 308.0788,
found 308.0771.
Compounds 19f-o were cyclized as described above for the
conversion of 21a to 19a .
C
15H20N6O6 364.1495, found 364.1513.
2-Am in o-5-p h en yl-3,7-dih ydr op yr r olo[2,3-d ]p yr im id in -
4-on e (19f): isolated in 42% yield as a light yellow solid: 1H
NMR (DMSO-d6) δ 11.19 (1 H, s), 10.31 (1 H, br s), 7.91 (2 H,
d, J ) 7.5 Hz), 7.26 (2 H, t, J ) 7.6 Hz), 7.12 (1 H, t, J ) 6.8
Hz), 7.03 (1 H, d, J ) 2.4 Hz), 6.11 (2 H, br s); 13C NMR
(DMSO-d6) δ 158.9, 152.45, 152.15, 134.7, 127.6, 127.2, 125.1,
119.4, 115.097.0; MS 227 (MH+).
2,4-Diam in o-5-ph en yl-7H-pyr r olo[2,3-d]pyr im idin e (19g):
isolated in 46% yield as a light yellow solid: 1H NMR (CD3-
OD) δ 7.45-7.40 (4 H, m), 7.33-7.29 (1 H, s), 6.79 (1 H, s);
2, 6-Dia m in o-5-[2-n it r o-1-(2-ch lor op h en yl)et h yl]-3 H -
p yr im id in -4-on e (21j): isolated in 81% yield as a light yellow
soild: mp 158 °C dec; IR (KBr) 3492, 3395, 3339, 3205, 2850,
1
1628, 1597, 1547, 1445, 1389, 1038, 794, 763 cm-1; H NMR
(DMSO-d6) δ 9.93 (1 H, s), 7.68 (1 H, d, J ) 7.5 Hz), 7.40 (1 H,
d, J ) 7.5 Hz), 7.25 (2 H, q, J ) 8.5 Hz), 6.19 (2 H, br s), 5.84
(2 H, br s), 5.54 (1 H, dd, J ) 13.0 and 7.5 Hz), 5.22 (1 H, dd,
J ) 13.0 and 7.5 Hz), 4.78 (1 H, t, J ) 7.5 Hz); 13C NMR
(DMSO-d6) δ 162.4, 153.8, 137.6, 132.6, 130.0, 129.2, 128.25,
126.9, 86.3, 75.8, 36.9; EIMS m/z 309 (M+), 291, 275, 262, 260,
9946 J . Org. Chem., Vol. 68, No. 26, 2003