March 2014
Synthesis and Biological Activity of Pyrido[4,3-d]pyrimidin-4(3H)-ones
289
8-Cyano-3-(4-fluorophenyl)-5-methyl-7-(methylthio)-2-(tert-
butylamino)-pyrido[4,3-d]pyrimidin-4(3H)-one (6d). This
3-(4-Chlorophenyl)-2-cyclohexylamino-8-cyano-5-methyl-7-
(methylthio)-pyrido[4,3-d]pyrimidin-4(3H)-one (6j). This com-
pound was obtained as white solid, mp >280ꢀC, yield 0.40 g,
compound was obtained as white solid, mp 278.0–278.9ꢀC,
yield 0.36 g, 91%; IR (KBr): 3416, 2928, 2213(CN), 1685
(C=O), 1564 cm-1; 1H NMR (CDCl3) d 1.45(s, 9H, 3*CH3),
2.68(s, 3H, SCH3), 2.87(s, 3H, py-CH3), 4.30(s, 1H, NH),
7.29 ~ 7.32 ppm (m, 4H, Ar-H). 13 C NMR(CDCl3) d 13.1,
26.4, 28.8, 53.9, 98.5, 108.0, 114.9, 117.9, 118.2, 129.6,
130.7, 151.8, 157.7, 161.6, 164.6, 167.2 ppm; Anal. Calcd for
C20H20FN5OS: C, 60.44; H, 5.07; N, 17.62. Found: C, 60.72;
H, 4.61; N, 17.30.
91%; 1 H NMR (CDCl3)
d 1.06 ~ 1.36(m, 4H, 2*CH2),
1.38 ~ 1.47(m, 2H, CH2), 1.59 ~1.62(m, 2H, CH2), 1.97 ~ 1.99(m,
2H, CH2), 2.68(s, 3H, SCH3), 2.87(s, 3H, CH3), 4.10 ~ 4.14(m,
1H, CH), 4.26(d, J =7.2 Hz, 1H, NH), 7.24 ~ 7.63 ppm (m, 4H,
Ar-H). ms: m/z 441 (M++2, 32), 440 (M++1, 18), 439 (M+, 83),
358 (93), 356 (100), 341 (15), 247 (8), 192 (19), 177(6), 152(7);
Anal. Calcd for C22H22ClN5OS: C, 60.06; H, 5.04; N, 15.92.
Found: C, 59.84; H, 4.44; N, 15.47.
8-Cyano-3-(4-fluorophenyl)-5-methyl-7-(methylthio)-2-
2-(2-Chlorobenzylamino)-8-cyano-5-methyl-7-(methylthio)-
3-phenyl-pyrido[4,3-d]pyrimidin-4(3H)-one (6k). This com-
pound was obtained as white solid, mp 202.9–204.9ꢀC, yield
0.38 g, 85%; IR (KBr): 3352, 2919, 2224(CN), 1688(C=O),
1557, 1532cm-1; 1 H NMR (CDCl3) d 2.68(s, 3H, SCH3), 2.87(s,
3H, py-CH3), 4.68(d, J = 6.4 Hz, 2H, NCH2), 5.31(s, 1H, NH),
7.17 ~ 7.80 ppm (m, 9H, Ar-H). ms: m/z 450 (M++3, 11), 449
(M++2, 41), 448 (M++1, 34), 447 (M+, 100), 446 (M+-1, 17), 412
(78), 322 (33), 140 (14); Anal. Calcd for C23H18ClN5OS: C,
61.67; H, 4.05; N, 15.63. Found: C, 61.84; H, 3.88; N, 15.24.
8-Cyano-2-(4-fluorobenzylamino)-5-methyl-7-(methylthio)-3-
phenyl-pyrido[4,3-d]pyrimidin-4(3H)-one (6l). This compound
was obtained as white solid, mp 230.0–232.0ꢀC, yield 0.35 g,
81%; IR (KBr): 3390, 2925, 2216(CN), 1684(C=O), 1556,
(pentylamino)-pyrido[4,3-d]pyrimidin-4(3H)-one (6e).
This
compound was obtained as white solid, mp 263.0–264.0ꢀC,
yield 0.35g, 85%; IR (KBr): 3356, 2857, 2220(CN), 1682(C=O),
1558, 1508cm-1; 1 H NMR (CDCl3) d 0.87(t, J = 7.2Hz, 3H,
CH3), 1.23 ~ 1.32(m, 4H, 2*CH2CH2), 1.52 ~1.55(m, 2H, CH2),
2.67(s, 3H, SCH3), 2.88(s, 3H, py-CH3), 3.50 ~ 3.53(m, 2H,
NCH2), 4.48(s, 1H, NH), 7.30 ~ 7.33 ppm (m, 4H, Ar-H). Anal.
Calcd for C21H22FN5OS: C, 61.29; H, 5.39; N, 17.02. Found: C,
61.20; H, 5.11; N, 16.76.
8-Cyano-3-(4-fluorophenyl)-2-(hexylamino)-5-methyl-7-
(methylthio)-pyrido[4,3-d]pyrimidin-4(3H)-one (6f).
This
compound was obtained as white solid, mp 162.0–164.0ꢀC;
yield 0.33g, 78%; IR (KBr): 3366, 2929, 2220(CN), 1683(C=O),
1558, 1532cm-1; 1 H NMR (CDCl3) d 0.86(t, J = 6.4Hz, 3H,
CH3), 1.26 ~ 1.53(m, 8H, 4*CH2), 2.68(s, 3H, SCH3), 2.89(s, 3H,
py-CH3), 3.50 ~ 3.53(m, 2H, NCH2), 4.42(s, 1H, NH),
7.29~ 7.35 ppm (m, 4H, Ar-H). Anal. Calcd for C22H24FN5OS:
C, 62.10; H, 5.68; N, 16.46. Found: C, 62.38; H, 5.35; N, 16.19.
2-Allylamino-8-cyano-3-(4-fluorophenyl)-5-methyl-7-
1
1529cm-1; H NMR (CDCl3) d 2.69(s, 3H, SCH3), 2.90(s, 3H,
py-CH3), 4.63(d, J = 5.6Hz, 2H, NCH2), 4.89(s, 1H, NH),
6.97 ~ 7.65 ppm (m, 9H, Ar-H). ms: m/z 433 (M++2, 10), 432
(M++1, 28), 431 (M+, 100), 430 (M+-1, 17), 322 (12), 185 (13);
Anal. Calcd for C23H18FN5OS: C, 64.02; H, 4.20; N, 16.23.
Found: C, 64.79; H, 3.98; N, 15.92.
(methylthio)-pyrido[4,3-d]pyrimidin-4(3H)-one (6g).
This
8-Cyano-5-methyl-2-(3-methylbenzylamino)-7-(methylthio)-
compound was obtained as white solid, mp 285.0–286.0ꢀC;
yield 0.33 g, 87%; 1 H NMR (CDCl3) d 2.63(s, 3H, SCH3),
2.78(s, 3H, CH3), 3.93 ~ 3.96(m, 2H, NCH2), 5.07(d,
J = 10 Hz, 1H, CH), 5.17(d, J = 16.8 Hz, 1H, CH), 5.81 ~ 5.85
(m, 1H, CH), 7.07(s, 1H, NH), 7.41 ~ 7.49 ppm (m, 4H, Ar-H).
ms: m/z 382 (M++1, 6), 381 (M+, 19), 380 (M+-1, 19), 366
(100), 348 (19), 340 (10), 204 (4), 190 (6), 135 (14); Anal.
Calcd for C19H16FN5OS: C, 59.83; H, 4.23; N, 18.36. Found:
C, 60.10; H, 4.22; N, 17.91.
3-phenyl-pyrido[4,3-d]pyrimidin-4(3H)-one (6m).
This com-
pound was obtained as white solid, mp 190.3–192.9ꢀC, yield
0.37 g, 87%; IR (KBr): 3429, 2922, 2215(CN), 1698(C=O), 1581,
1540cm-1; 1 H NMR (CDCl3) d 2.33(s, 3H, CH3), 2.68(s, 3H,
SCH3), 2.89(s, 3H, py-CH3), 4.65(d, J =5.6 Hz, 2H, CH2), 4.86(s,
1H, NH), 7.07 ~ 7.64 ppm (m, 9H, Ar-H). ms: m/z 429 (M++2, 9),
428 (M++1, 29), 427 (M+, 100), 426 (M+-1, 16), 322 (14), 196
(33), 120 (32); Anal. Calcd for C24H21N5OS: C, 67.43; H, 4.95;
N, 16.38. Found: C, 67.89; H, 4.77; N, 16.18.
3-(4-Chlorophenyl)-8-cyano-5-methyl-7-(methylthio)-2-
8-Cyano-2-(4-fluorophenethylamino)-5-methyl-7-(methylthio)-
propylamino-pyrido[4,3-d]pyrimidin-4(3H)-one (6h).
This
3-phenyl-pyrido[4,3-d]pyrimidin-4(3H)-one (6n).
This com-
compound was obtained as white solid, mp 235.0–238.0ꢀC,
pound was obtained as white solid, mp 207.0–208.7ꢀC, yield
0.37 g, 83%; IR (KBr): 3429, 2928, 2222(CN), 1693(C=O), 1557,
1535cm-1; 1H NMR (CDCl3) d 2.69(s, 3H, SCH3), 2.86(t,
J = 7.2 Hz, 2H, CH2), 2.89(s, 3H, py-CH3), 3.70–3.72(m, 2H,
NCH2), 4.46(s, 1H, NH), 6.91 ~ 7.58 ppm (m, 9H, Ar-H). ms: m/z
447 (M++2, 5), 446 (M++1, 14), 445 (M+, 63), 425 (20), 322
(100), 307 (7), 122 (50); Anal. Calcd for C24H20FN5OS: C, 64.70;
H, 4.52; N, 15.72. Found: C, 64.67; H, 4.17; N, 15.30.
1
yield 0.33 g, 83%; H NMR (CDCl3) d 0.88(t, J = 7.2 Hz, 3H,
CH3), 1.55 ~ 1.61(m, 2H, CH2), 2.68(s, 3H, SCH3), 2.89(s,
3H, py-CH3), 3.51 ~ 3.53(m, 2H, NCH2), 4.46(s, 1H, NH),
7.25 ~ 7.63 ppm (m, 4H, Ar-H). ms: m/z 401 (M++2, 37), 400
(M++1, 26), 399 (M+, 96), 356 (100), 341 (9), 246 (7), 231
(8), 204 (10), 152 (21); Anal. Calcd for C19H18ClN5OS: C,
57.07; H, 4.54; N, 17.51. Found: C, 57.25; H, 4.56; N, 16.94.
3-(4-Chlorophenyl)-8-cyano-2-butylamino-5-methyl-7-
8-Cyano-2-(3-methoxyphenethylamino)-5-methyl-7-(methylthio)-
(methylthio)-pyrido[4,3-d]pyrimidin-4(3H)-one (6i).
This
3-phenyl-pyrido[4,3-d]pyrimidin-4(3H)-one (6o).
This com-
compound was obtained as white solid, mp 233.0–234.0ꢀC,
yield 0.34 g, 82%; 1 H NMR (CDCl3) d 0.91(t, J = 7.2 Hz, 3H,
CH3), 1.24 ~ 1.32(m, 2H, CH2), 1.49 ~ 1.56(m, 2H, CH2), 2.68
(s, 3H, SCH3), 2.88(s, 3H, py-CH3), 3.53 ~ 3.55(m, 2H,
NCH2), 4.44(s, 1H, NH), 7.25 ~ 7.63 ppm (m, 4H, Ar-H). ms:
m/z 415 (M++2, 8), 414 (M++1, 26), 413 (M+, 100), 322 (34),
204 (52), 182 (55), 167 (67), 106 (31), 91 (65), 77(20); Anal.
Calcd for C20H20ClN5OS: C, 58.03; H, 4.87; N, 16.92. Found:
C, 58.12; H, 4.41; N, 16.61.
pound was obtained as white solid, mp 185.5–188.5ꢀC, yield
0.36 g, 79%; IR (KBr): 3412, 2931, 2219(CN), 1689(C=O), 1556,
1535cm-1; 1H NMR (CDCl3) d 2.69(s, 3H, SCH3), 2.85(t,
J = 6.4 Hz, 2H, CH2), 2.90(s, 3H, py-CH3), 3.72 ~ 3.75(m, 2H,
NCH2), 3.79(s, 3H, OCH3), 4.47(s, 1H, NH), 6.61 ~ 7.54 ppm (m,
9H, Ar-H). ms: m/z 459 (M++2, 4), 458 (M++1, 13), 457 (M+,
41), 322 (35), 307 (10), 134 (100), 91 (23), 77(23); Anal. Calcd
for C25H23N5O2S: C, 65.63; H, 5.07; N, 15.31. Found: C, 65.48;
H, 4.97; N, 15.07.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet