828
D. V. Tinh and W. Stadlbauer
Vol 45
7-Amino-1,3-dimethyl-5-phenylaminopyrido[2,3-d]pyrimi-
dine-2,4(1H,3H)-dione (12a). From 11a (5.57 g, 10 mmol); ir:
5-Benzylamino-1,3,8-trimethyl-2,4,7-trioxo-1,2,3,4,7,8-
hexahydropyrido[2,3-d]pyrimidine-6-carbaldehyde (15a).
From 13a (2.83 g, 10 mmol) and benzylamine (3b) (1.28 g, 12
1
3440 m, 3340 m, 3230 w, 1690 s, 1635 s cm-1; H nmr (DMSO-
1
mmol); ir: 3080 w, 1715 s, 1665 s, 1640 s cm-1; H nmr: δ 3.35,
d6): δ 3.25 and 3.47 (2 s, 2x3 H, 2 NMe), 5.90 (s, 1 H, 6-H), 6.66
(s, 2 H, 7-NH2), 7.18-7.33 (m, 3 H, ArH), 7.40-7.50 (m, 2 H,
ArH), 10.64 (s, 1 H, 5-NH). Anal. Calcd. for C15H15N5O2
(297.32): C, 60.60; H, 5.09; N, 23.55. Found: C, 60.43; H, 5.12;
N, 23.78.
3.50 and 3.55 (3 s, 3x3 H, 3 NMe), 4.22 (d, J = 5 Hz, 2 H,
benzyl-CH2), 7.25-7.32 (m, 5 H, ArH), 10.10 (s, 1 H, CH=O),
10.58 (t, J = 4.5 Hz, 1 H, NH). Anal. Calcd. for C18H18N4O4
(354.37): C, 61.01; H, 5.12; N, 15.81. Found: C, 60.80; H, 4.95;
N, 15.79.
7-Amino-1,3-diphenyl-5-phenylaminopyrido[2,3-d]pyrimi-
dine-2,4(1H,3H)-dione (12b). From 11b (6.82 g, 10 mmol); ir:
5-Benzylamino-1,3dimethyl-2,4,7-trioxo-8-phenyl-1,2,3,4,
7,8-hexahydropyrido[2,3-d]pyrimidine-6-carbaldehyde (15b).
From 13b (3.45 g, 10 mmol) and benzylamine (3b) (1.28 g, 12
1
3470 m, 3340 m, 1710 s, 1615 s cm-1; H nmr (DMSO-d6): δ
4.48 (s, 2 H, 7-NH2), 5.80 (s, 1 H, 6-H), 7.20-7.50 (m, 15 H,
ArH), 10.60 (s, 1 H, 5-NH). Anal. Calcd. for C25H19N5O2
(421.46): C, 71.25; H, 4.54; N, 16.62. Found: C, 70.97; H, 4.42;
N, 16.40.
7-Amino-5-benzylamino-1,3-dimethylpyrido[2,3-d]pyrimi-
dine-2,4(1H,3H)-dione (12c). From 11c (5.71 g, 10 mmol); ir:
3480 w, 3430 w, 3340 m, 3230 w, 1670 s, 1645 s, 1620 s cm-1;
1H nmr (DMSO-d6): δ 3.21 and 3.43 (2 s, 2x3 H, NMe), 4.39 (d,
J = 5 Hz, 2 H, CH2), 5.40 (s, 1 H, 6-H), 6.53 (s, 2 H, 7-NH2),
7.32-7.38 (m, 5 H, ArH), 9.15 (t, J = 4.5 Hz, 1 H, 5-NH). Anal.
Calcd. for C16H17N5O2 (311.35): C, 61.72; H, 5.50; N, 22.49.
Found: C, 61.02; H, 5.39; N, 22.28.
1
mmol); ir: 3150 w, 3080 w, 1710 s, 1670 s, 1655 m cm-1; H
nmr: δ 2.85 and 3.35 (2 s, 2x3 H, 2 NMe), 4.44 (d, J = 5 Hz, 2
H, benzyl-CH2), 7.30-7.50 (m, 10 H, ArH), 10.10 (s, 1 H,
CH=O), 10.80 (t, J = 4.5 Hz, 1 H, NH). Anal. Calcd. for
C23H20N4O4 (416.44): C, 66.34; H, 4.84; N, 13.45. Found: C,
66.13; H, 4.73; N, 13.43.
1,3-Dimethyl-2,4,7-trioxo-8-phenyl-5-[(pyridin-3-ylmethyl)-
amino]-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-6-car-
baldehyde (15c). From 13b (3.45 g, 10 mmol) and 3-picolyl-
amine (3c) (1.29 g, 12 mmol); ir: 1720 s, 1670 s, 1650 s cm-1; 1H
nmr: δ 2.87 and 3.40 (2 s, 2x3 H, 2 NMe), 4.50 (d, J = 5 Hz, 2
H, CH2), 7.25-7.35 (m, 3 H, ArH and 5'-H of pyridyl), 7.48-7.52
(m, 3 H, ArH), 7.70 (d, J = 8 Hz, 2 H, 4'-H and 6'-H of pyridyl),
8.62 (s, 1 H, 2'-H of pyridyl), 10.10 (s, CH=O). Anal. Calcd. for
C22H19N5O4 (417.43): C, 63.30; H, 4.59; N, 16.78. Found: C,
62.94; H, 4.58; N, 16.45.
7-Amino-5-benzylamino-1,3-diphenyl-pyrido[2,3-d]pyrim-
idine-2,4(1H,3H)-dione (12d). From 11d (6.96 g, 10 mmol); ir:
1
3500 w, 3390 m, 3300 w, 1700 s, 1640, 1600 s cm-1; H nmr
(DMSO-d6): δ 4.40 (d, J = 5 Hz, 2 H, CH2), 5.44 (s, 1 H, 6-H),
6.32 (s, 2 H, 7-NH2), 7.32-7.52 (m, 15 H, ArH), 9.05 (t, J = 4.5
Hz, 1 H, 5-NH). Anal. Calcd. for C26H21N5O2 (435.49): C, 71.71;
H, 4.86; N, 16.08. Found: C, 71.41; H, 4.82; N, 16.07.
General Procedure for the Preparation of 5-Aminosubsti-
tuted 2,4,7-Trioxo-8-phenyl-1,2,3,4,7,8-hexahydropyrido[2,3-
1,3,8-Trimethyl-2,4,7-trioxo-5-piperidin-1-yl-1,2,3,4,7,8-
hexahydropyrido[2,3-d]pyrimidine-6-carbaldehyde (16a).
From 13a (2.83 g, 10 mmol) and piperidine (6a) (1.02 g, 12
mmol); ir: 3400 w, 2940 w, 2850 w, 1710 s, 1670 s, 1640 s cm-1;
1H nmr: δ 1.67 (m, 6 H 3,4,5-piperidinyl-CH2), 3.30 (m, 4 H,
2,6-piperidinyl-CH2), 3.32, 3.48 and 3.50 (3 s, 3x3 H, 3 NMe),
9.83 (s, 1 H, CH=O). Anal. Calcd. for C16H20N4O4 (332.36): C,
57.82; H, 6.07; N, 16.86. Found: C, 57.43; H, 5.99; N, 16.67.
1,3-Dimethyl-2,4,7-trioxo-8-phenyl-5-piperidin-1-yl-1,2,3,
4,7,8-hexahydropyrido[2,3-d]pyrimidine-6-carbaldehyde
(16b). From 13b (3.45 g, 10 mmol) and piperidine (6a) (1.02 g,
12 mmol); ir: 3060 w, 2930 w, 2850 w, 1720 s, 1680 s, 1655 s
d]pyrimidine-6-carbaldehydes 14-16.
A mixture of the
appropriate 5-chloropyrido[2,3-d]pyrimidine-trione 13 [4b] (10
mmol) and amine 3 (12 mmol) in dimethyl-formamide (15 mL)
was stirred fro 1-2 hours at 70-80 °C. The solvent was removed
in vacuo, and the residual product triturated with water (100
mL). The resulting precipitate was filtered and washed with
water to give yellow prisms. Further data: see Table 2.
Table 2
1
cm-1; H nmr: δ 1.75 (m, 6 H, 3,4,5-piperidinyl-CH2), 2.85 and
Chemical Yields and Mp for Compounds 14-16.
3.39 (2 s, 2x 3 H, 2 NMe), 3.51 (m, 4 H, 2,6-piperidinyl-CH2),
7.25-7.50 (m, 5 H, ArH), 9.80 (s, 1 H, CH=O). Anal. Calcd. for
C21H22N4O4 (394.43): C, 63.95; H, 5.62; N, 14.20. Found: C,
63.73; H, 5.57; N, 14.27.
Yield
Mp (°C)
232-234
205-207
214-216
233-235
167-169
265-267
194-196
273-275
Recryst. Solvent
ethanol
14
3.53 g (82%)
2.83 g (80%)
3.41 g (82%)
2.50 g (60%)
2.87 g (86%)
3.39 g (86%)
2.70 g (81%)
3.37 g (85%)
15a
15b
15c
16a
16b
16c
16d
ethanol
1,3,8-Trimethyl-5-morpholin-4-yl-2,4,7-trioxo-1,2,3,4,7,8-
hexahydropyrido[2,3-d]pyrimidine-6-carbaldehyde
DMF/ ethanol
ethanol
(16c).
From 13a (2.83 g, 10 mmol) and morpholine (6b) (1.03 g, 12
mmol); ir: 2970 w, 1710 s, 1675 s, 1650 s, 1635 s cm-1; 1H nmr:
δ 3.33 (t, J = 4.5 Hz, 4 H, 3,5-morpholinyl-CH2), 3.51, 3.52 and
3.53 (3 s, 3x3 H, 3 NMe), 3.92 (t, J = 4.5 Hz, 4 H, 2,6-
morpholinyl-CH2), 9.92 (s, 1 H, CH=O). Anal. Calcd. for
C15H18N4O5 (334.33): C, 53.89; H, 5.43; N, 16.76. Found: C,
53.72; H, 5.57; N, 16.75.
1,3-Dimethyl-5-morpholin-4-yl-2,4,7-trioxo-8-phenyl-1,2,3,
4,7,8-hexahydropyrido[2,3-d]pyrimidine-6-carbaldehyde (16d).
From 13b (3.45 g, 10 mmol) and morpholine (6b) (1.03 g, 12
mmol); ir: 3060 w, 2980 w, 2850 w, 1720 s, 1675 s, 1650 s cm-1;
1H nmr (DMSO-d6) δ 2.62 and 3.20 (2 s, 2x3 H, NMe), 3.47 (t, J
= 4.5 Hz, 4 H, 3,5-morpholinyl-CH2), 3.82 (t, J = 4.5 Hz, 4 H,
2,6-morpholinyl-CH2), 7.52 (m, 5 H, ArH), 9.61 (s, 1 H, CH=O).
ethanol
dimethylformamide
ethanol
dimethylformamide
5-(2,6-Dimethylphenylamino)-1,3-dimethyl-2,4,7-trioxo-8-
phenyl-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidine-6-car-
baldehyde (14). From 13b (3.45 g, 10 mmol) and 2,6-
dimethylaniline (13d) (1.45 g, 12 mmol); ir: 1720 s, 1670 s,
1610 s cm-1; H nmr: δ 2.16 (s, 6 H, 2 Me), 2.90 and 3.47 (2 s,
1
2x3 H, 2 NMe), 7.09 (s, 3 H, ArH), 7.30-7.50 (m, 5 H, ArH),
9.63 (s, 1 H, CH=O), 11.88 (s, 1 H, NH). Anal. Calcd. for
C24H22N4O4 (430.47): C, 66.97; H, 5.15; N, 13.02. Found: C,
66.82; H, 5.12; N, 13.04.