Arch. Pharm. Chem. Life Sci. 2011, 344, 675–683
Synthesis of Novel Thiazolyl-Pyrimidines
681
J ¼ 5.2 Hz, Py-H), 8.01 (s, 1H, NH), 7.35–7.28 (m, 4H, Ar-H), 7.15–
7.07 (m, 3H, Ar-H), 6.91 (d, 1H, J ¼ 6.0 Hz, Ar-H), 6.83 (d, 1H,
J ¼ 5.6 Hz, Py-H), 3.50 (s, 3H, CH3), 2.62 (s, 3H, CH3), 2.29 (s, 3H,
CH3). EIMS m/z (%): 421 (Mþ, 100), 406 (32), 388 (15), 303 (13), 284
(18), 256 (14), 241 (10), 213 (10), 185 (14), 171 (11), 157 (8), 129 (28),
118 (10), 105 (15), 97 (18), 83 (21), 73 (60), 55 (53). Anal. calcd. for
C22H20ClN5S: C, 62.62; H, 4.78; N, 16.60; Found: C, 62.36; H, 4.62;
N, 16.51.
(4-{2-[(4-Chloro-phenyl)-methyl-amino]-4-methyl-thiazol-
5-yl}-pyrimidin-2-yl)-(4-fluoro-phenyl)-amine 29
Yield 69.3%. M.p. 216–2178C. IR: nmax (KBr) cmꢀ1: 3423, 3264, 3222,
3050, 1625, 1578, 1539, 1493, 1427, 1399, 1369, 1337. 1H-NMR
(CDCl3, TMS, 400 MHz, d ppm): 8.25 (s, 1H, J ¼ 5.2 Hz, Py-H), 7.53–
7.50 (m, 2H, Ar-H), 7.40 (dd, 4H, J1 ¼ 8.4 Hz, J2 ¼ 8.8 Hz, Ar-H),
7.16 (s, 1H, NH), 6.98 (t, 2H, J ¼ 8.4 Hz, Ar-H), 6.81 (s, 1H,
J ¼ 5.2 Hz, Py-H), 3.55 (s, 3H, CH3), 2.59 (s, 3H, CH3). EIMS m/z
(%): 425 (Mþ, 100), 299 (22), 258 (10), 226 (19), 212 (9), 111 (8), 95 (9),
83 (8), 57 (8). Anal. calcd. for C21H17ClFN5S: C, 59.22; H, 4.02;
N, 16.44; Found: C, 59.36; H, 4.13; N, 16.62.
(4-{2-[(4-Chloro-phenyl)-methyl-amino]-4-methyl-thiazol-
5-yl}-pyrimidin-2-yl)-phenyl-amine 25
Yield 23.2%. M.p. 203–2058C. IR: nmax (KBr) cmꢀ1: 3426, 3258,
3188, 3044, 1617, 1571, 1541, 1488, 1447, 1403, 1367, 1341.
1H-NMR (CDCl3, TMS, 400 MHz, d ppm): 8.28 (d, 1H, J ¼ 5.2 Hz,
Py-H), 7.58 (d, 2H, J ¼ 7.6 Hz, Ar-H), 7.44–7.36 (m, 4H, Ar-H), 7.32–
7.29 (m, 2H, Ar-H), 7.03 (t, 1H, J ¼ 7.2 Hz, Ar-H), 6.83 (d, 1H,
J ¼ 5.6 Hz, Py-H), 3.55 (s, 3H, CH3), 2.60 (s, 3H, CH3). EIMS m/z
(%): 407 (Mþ, 100), 392 (9), 372 (5), 281 (35), 267 (7), 240 (14), 208
(27). Anal. calcd. for C21H18ClN5S: C, 61.83; H, 4.45; N, 17.17;
Found: C, 61.75; H, 4.35; N, 17.29.
(4-{2-[(2-Chloro-phenyl)-methyl-amino]-4-methyl-thiazol-
5-yl}-pyrimidin-2-yl)-phenyl-amine 30
Yield 40.8%. M.p. 168–1708C. IR: nmax (KBr) cmꢀ1: 3416, 3267,
3192, 3115, 3059, 3034, 2927, 2860, 1934, 1934, 1611, 1580,
1537, 1499, 1434, 1402, 1370, 1338. 1H-NMR (CDCl3, TMS,
400 MHz, d ppm): 8.27 (s, 1H, J ¼ 5.2 Hz, Py-H), 7.58–7.54
(m, 3H, Ar-H), 7.46–7.45 (m, 1H, Ar-H), 7.41–7.39 (m, 2H, Ar-H),
7.24–7.22 (m, 1H, Ar-H), 7.02–6.97 (m, 2H, Ar-H), 6.80 (d, 1H,
J ¼ 5.2 Hz, Py-H), 3.51 (s, 3H, CH3), 2.61 (s, 3H, CH3). EIMS m/z
(%): 407 (Mþ, 91), 372 (100), 240 (12), 238 (8), 208 (20), 186 (44), 77
(19). Anal. calcd. for C21H18ClN5S: C, 61.83; H, 4.45; N, 17.17;
Found: C, 61.79; H, 4.63; N, 17.11.
(4-{2-[(4-Chloro-phenyl)-methyl-amino]-4-methyl-thiazol-
5-yl}-pyrimidin-2-yl)-m-tolyl-amine 26
Yield 17.5%. M.p. 205–2088C. IR: nmax (KBr) cmꢀ1: 3425, 3280,
1601, 1580, 1561, 1539, 1490, 1425, 1401, 1368, 1336. 1H-NMR
(CDCl3, TMS, 400 MHz, d ppm): 8.27 (d, 1H, J ¼ 5.6 Hz, Py-H), 7.65
(s, 1H, Ar-H), 7.40 (dd, 4H, J1 ¼ 8.8 Hz, J2 ¼ 8.8 Hz, Ar-H), 7.15
(d, 3H, J ¼ 4.8 Hz, Ar-H), 6.83 (d, 1H, J ¼ 5.6 Hz, Py-H), 3.55 (s, 3H,
CH3), 2.60 (s, 3H, CH3), 2.24 (s, 3H, CH3). EIMS m/z (%): 421
(Mþ, 100), 406 (10), 295 (23), 254 (11), 222 (17), 207 (10). Anal.
calcd. for C22H20ClN5S: C, 62.62; H, 4.78; N, 16.60; Found: C,
62.79; H, 4.67; N, 16.51.
(4-{2-[(2-Chloro-phenyl)-methyl-amino]-4-methyl-thiazol-
5-yl}-pyrimidin-2-yl)-m-tolyl-amine 31
Yield 56.7%. M.p. 189–1918C. IR: nmax (KBr) cmꢀ1: 3425, 3269,
3200, 3068, 1925, 1752, 1601, 1580, 1563, 1541, 1505, 1423,
1401, 1367, 1336. 1H-NMR (CDCl3, TMS, 400 MHz, d ppm): 8.23
(brs, 1H, Py-H), 7.64 (s, 1H, NH), 7.58–7.56 (m, 1H, Ar-H), 7.45–7.39
(m, 3H, Ar-H), 7.22–7.12 (m, 3H, Ar-H), 6.81 (d, 1H, J ¼ 5.6 Hz,
Py-H), 6.79 (mꢁ, 1H, Ar-H), 3.52 (s, 3H, CH3), 2.62 (s, 3H, CH3), 2.17
(s, 3H, CH3) (ꢁ overlapped with Py-H). EIMS m/z (%): 421 (Mþ, 100),
406 (11), 386 (90), 254 (10), 222 (13), 207 (9), 193 (15), 186 (33), 129
(12), 111 (10), 91 (13), 73 (19), 57 (23). Anal. calcd. for C22H20ClN5S:
C, 62.62; H, 4.78; N, 16.60; Found: C, 62.71; H, 4.64; N, 16.37.
(4-{2-[(4-Chloro-phenyl)-methyl-amino]-4-methyl-thiazol-
5-yl}-pyrimidin-2-yl)-(3-chloro-phenyl)-amine 27
Yield 50.1%. M.p. 226–2298C. IR: nmax (KBr) cmꢀ1: 3424, 3266,
3184, 3109, 1614, 1595, 1575, 1532, 1486, 1424, 1365, 1338.
1H-NMR (CDCl3, TMS, 400 MHz, d ppm): 8.18 (d, 1H, J ¼ 5.2 Hz,
Py-H), 8.06 (s, 1H, NH), 7.44–7.34 (m, 4H, Ar-H), 7.17–7.02 (m, 4H,
Ar-H), 6.89 (d, 1H, J ¼ 5.6 Hz, Py-H), 3.58 (s, 3H, CH3), 2.63 (s, 3H,
CH3). EIMS m/z (%): 441 (Mþ, 100), 406 (8), 315 (66), 303 (15), 274
(13), 242 (16), 207 (28), 202 (11), 164 (11), 125 (11), 75 (8). Anal.
calcd. for C21H17Cl2N5S: C, 57.02; H, 3.87; N, 15.83; Found: C,
57.21; H, 3.73; N, 15.95.
(4-{2-[(2-Chloro-phenyl)-methyl-amino]-4-methyl-thiazol-
5-yl}-pyrimidin-2-yl)-(3-chloro-phenyl)-amine 32
Yield 53%. M.p. 195–1988C. IR: nmax (KBr) cmꢀ1: 3417, 3261, 3180,
3067, 3005, 1815, 1747, 1608, 1576, 1503, 1419, 1368, 1536.
1H-NMR (CDCl3, TMS, 400 MHz, d ppm): 8.28 (s, 1H, J ¼ 5.2 Hz,
Py-H), 8.03 (s, 1H, NH), 7.57–7.55 (m, 1H, Ar-H), 7.47–7.45 (m, 1H,
Ar-H), 7.39–7.38 (m, 2H, Ar-H), 7.16–7.08 (m, 3H, Ar-H), 6.92 (d, 1H,
J ¼ 7.2 Hz, Ar-H), 6.86 (d, 1H, J ¼ 5.6 Hz, Py-H), 3.52 (s, 3H, CH3),
2.62 (s, 3H, CH3). EIMS m/z (%): 441 (M þ, 67), 406 (100), 331 (10),
296 (13), 256 (11), 207 (13), 186 (35), 164 (9), 129 (15), 111 (16), 97
(14), 85 (15), 73 (32), 57 (35). Anal. calcd. for C21H17Cl2N5S:
C, 57.02; H, 3.87; N, 15.83; Found: C, 57.15; H, 3.95; N, 15.79.
(4-{2-[(4-Chloro-phenyl)-methyl-amino]-4-methyl-thiazol-
5-yl}-pyrimidin-2-yl)-(3-methoxy-phenyl)-amine 28
Yield 60%. M.p. 180–1838C. IR: nmax (KBr) cmꢀ1: 3419, 3280, 3197,
3121, 3067, 3053, 1598, 1583, 1561, 1537, 1491, 1456, 1429,
1401, 1369, 1338. 1H-NMR (CDCl3, TMS, 400 MHz, d ppm): 8.28
(s, 1H, J ¼ 4.4 Hz, Py-H), 7.49 (s, 1H, NH), 7.40 (dd, 4H, J1 ¼ 8.0 Hz,
J2 ¼ 8.0 Hz, Ar-H), 7.16 (t, 2H, J ¼ 8.0 Hz, Ar-H), 6.92 (d, 1H,
J ¼ 7.6 Hz, Ar-H), 6.85 (d, 1H, J ¼ 4.8 Hz, Py-H), 6.57 (d, 1H,
J ¼ 8.0 Hz, Ar-H), 3.71 (s, 3H, OCH3), 3.54 (s, 3H, CH3), 2.59
(s, 3H, CH3). EIMS m/z (%): 437 (Mþ, 100), 422 (8), 403 (10),
311 (10), 284 (9), 270 (9), 256 (9), 238 (10), 185 (9), 129 (17),
111 (14), 97 (20), 83 (21), 73 (33), 55 (48). Anal. calcd. for
C22H20ClN5OS: C, 60.34; H, 4.60; N, 15.99; Found: C, 60.52;
H, 4.71; N, 15.87.
(4-{2-[(2-Chloro-phenyl)-methyl-amino]-4-methyl-thiazol-
5-yl}-pyrimidin-2-yl)-(3-methoxy-phenyl)-amine 33
Yield 43.6%. M.p. 165–1678C. IR: nmax (KBr) cmꢀ1: 3424, 3282, 3212,
3114, 3012, 1585, 1538, 1503, 1462, 1424, 1399, 1368, 1337.
1H-NMR (CDCl3, TMS, 400 MHz, d ppm): 8.28 (brs, 1H, Py-H),
7.57–6.85 (m, 8H, Ar-H), 6.52 (brs,1H, Py-H), 3.64 (s, 3H, OCH3),
3.50 (s, 3H, CH3), 2.61 (s, 3H, CH3). EIMS m/z (%): 437 (Mþ, 100), 402
(72), 256 (11), 201 (12), 185 (16), 129 (13), 111 (12), 97 (18), 83 (17), 73
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