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5.2.14. N2-(2-furanylmethyl)-N4-((4-methyl-2-phenyl-5-thiazolyl)
methyl)pyrimidine-2,4-diamine (8m)
Compound 8m (77% yield) was prepared according to the
method described for the preparation of compound 8b except using
furfurylamine instead of ethylamine. 1H NMR (500 MHz, DMSO-d6)
J ¼ 6.1 Hz, 2H, CH2CH(CH3)2), 2.43 (s, 3H, CH3), 1.85e1.77 (m, 1H,
CH(CH3)2), 0.85 (d, J ¼ 6.5 Hz, 6H, CH(CH3)2). 13C NMR (125 MHz,
DMSO-d6): d 162.13, 161.88, 161.44, 155.28, 149.39, 134.27, 132.10,
129.16, 127.28, 125.61, 95.00, 48.27, 36.30, 27.89, 20.26, 15.00. HPLC
purity: 98.5%, tR
¼
7.054 min. HRMS (ESI): calcd for
d
7.83 (d, J ¼ 7.7 Hz, 2H, H-20 and H-60 AreH), 7.74 (d, J ¼ 6.6 Hz, 1H,
[C19H22ClN5S þ H]þ 388.1357, found 388.1393.
H-6 pyrimidine), 7.60 (s, 1H, H-5 furan), 7.47e7.46 (m, 3H, H-30, H-
40and H-50 AreH), 6.41 (s, 1H, H-4 furan), 6.35 (s, 1H, H-3 furan),
6.08 (d, J ¼ 5.8 Hz, 1H, H-5 pyrimidine), 4.76 (s, 2H, furan-CH2), 4.66
(s, 2H, thiazole-CH2), 2.43 (s, 3H, CH3). 13C NMR (125 MHz, DMSO-
5.2.18. N4-((2-(2-(benzyloxy)phenyl)-4-methyl-5-thiazolyl)
methyl)-N2-isobutylpyrimidine-2,4-diamine (9d)
Compound 9d (84% yield) was prepared according to the
method described for the preparation of compound 9a except using
2-(benzyloxy)benzonitrile instead of 2-chlorobenzonitrile. 1H NMR
d6):
d 164.25, 164.01, 161.93, 161.86, 158.78, 150.57, 142.43, 133.00,
130.06, 129.17, 125.78, 114.11, 110.53, 107.37, 95.32, 37.36, 35.45,
15.01. HPLC purity: 96.9%, tR ¼ 5.288 min. HRMS (ESI): calcd for
[C20H19N5OS þ H]þ 378.1383, found 378.1414.
(500 MHz, DMSO-d6)
d
7.76 (d, J ¼ 8.7 Hz, 2H, H-200 and H-600
OCH2AreH), 7.65 (d, J ¼ 5.6 Hz, 1H, H-6 pyrimidine), 7.46 (d,
J ¼ 7.4 Hz, 2H, H-30 and H-60 AreH), 7.40 (dd, J ¼ 7.4, 7.6 Hz, 2H, H-40
and H-50 AreH), 7.34 (dd, J ¼ 7.3, 7.1 Hz, 1H, H-400 OCH2AreH), 7.08
(d, J ¼ 8.7 Hz, 2H, H-300 and H-500 OCH2AreH), 5.75 (d, J ¼ 5.9 Hz, 1H,
H-5 pyrimidine), 5.15 (s, 2H, OCH2Ar), 4.59 (s, 2H, CH2), 3.08 (m, 2H,
CH2CH(CH3)2), 2.39 (s, 3H, CH3), 1.88e1.80 (m, 1H, CH(CH3)2), 0.86
(d, J ¼ 6.7 Hz, 6H, CH(CH3)2). 13C NMR (125 MHz, DMSO-d6):
5.2.15. N4-((2-(2-chlorophenyl)-4-methyl-5-thiazolyl)methyl)-N2-
isobutylpyrimidine-2,4-diamine (9a)
To a mixture of 2-chlorobenzonitrile 2a (1.37 g, 10.0 mmol) and
CaH2 (842 mg, 20.0 mmol) was taken in a two-necked 50 ml round-
bottomed flask, and the content was cooled to 0 ꢀC and added
thioacetic acid (5 ml). After stirring for 15 min, the reaction mixture
was heated in an oil bath at 80 ꢀC for 3 h. After the completion of
the reaction, the contents were cooled to r.t., the solution was
concentrated under vacuum and the residue partitioned between
EtOAc and water. The organic phase was washed with water and
brine, dried (MgSO4), filtered, concentrated, and purified by crys-
tallization using PE and EtOAc (9:1) to afford 2-chlorothiobenzamid
3a (1.65 g, 96%). Compound 9a (78% yield) was prepared according
to the method described for the preparation of compound 8f except
using 2-chlorothiobenzamide 3a instead of thiobenzamide 3l. 1H
d
164.11, 163.07, 161.89, 157.91, 154.57, 149.02 147.72, 136.26, 130.43,
128.33, 127.95, 127.68, 127.40, 122.01, 120.98, 113.48, 95.59, 69.90,
48.06, 35.19, 27.80, 20.13, 14.98. HPLC purity: 99.1%, tR ¼ 6.543 min.
HRMS (ESI): calcd for [C26H29N5OS
460.2206.
þ
H]þ 460.2166, found,
5.2.19. N4-((2-(3-(benzyloxy)phenyl)-4-methyl-5-thiazolyl)
methyl)-N2-isobutylpyrimidine-2,4-diamine (9e)
Compound 9e (87% yield) was prepared according to the
method described for the preparation of compound 9a except using
3-(benzyloxy)benzonitrile instead of 2-chlorobenzonitrile. 1H NMR
NMR (500 MHz, DMSO-d6)
d
8.13 (d, J ¼ 7.0 Hz, 1H, H-60 AreH), 7.64
(d, J ¼ 5.0 Hz, 1H, H-6 pyrimidine), 7.59 (d, J ¼ 7.8 Hz, 1H, H-30
AreH), 7.45 (d, J ¼ 7.8 Hz, 2H, H-40 and H-50AreH), 6.50 (br s, 1H,
NH-2), 5.71 (d, J ¼ 5.5 Hz, 1H, H-5 pyrimidine), 4.63 (d, J ¼ 5.7 Hz,
2H, CH2), 3.06 (t, J ¼ 5.5 Hz, 2H, CH2CH(CH3)2), 2.46 (s, 3H, CH3),
(500 MHz, CDCl3) d
7.77 (s, 1H, H-6 pyrimidine), 7.54 (s, 1H, H-20
AreH), 7.46e7.44 (m, 3H, H-50 and H-60AreH and H-400 OCH2AreH),
7.39 (dd, J ¼ 7.7, 7.2 Hz, 2H, H-200 and H-600 OCH2AreH), 7.32 (dd,
J ¼ 8.8, 7.7 Hz, 2H, H-300 and H-500 OCH2AreH), 7.01 (d, J ¼ 8.2 Hz,1H,
H-40 AreH), 5.73 (d, J ¼ 5.9 Hz, 1H, H-5 pyrimidine), 5.12 (s, 2H,
OCH2Ar), 4.69 (s, 2H, CH2), 3.25 (t, J ¼ 6.3 Hz, 2H, CH2CH(CH3)2),
2.48 (s, 3H, CH3), 1.93e1.85 (m, 1H, CH(CH3)2), 0.97 (d, J ¼ 6.7 Hz,
1.87e1.80 (m, 1H, CH(CH3)2), 0.84 (d, J ¼ 6.7 Hz, 6H, CH(CH3)2). 13
C
NMR (125 MHz, DMSO-d6):
d 162.21, 161.88, 158.72, 148.27, 133.13,
131.41, 130.73, 133.68, 130.33, 130.17, 127.65, 127.61, 95.36, 48.29,
34.94, 27.86, 20.28, 14.90. HPLC purity: 97.3%, tR ¼ 5.990 min. HRMS
(ESI): calcd for [C19H22ClN5S þ H]þ 388.1357, found 388.1381.
6H, CH(CH3)2). 13C NMR (125 MHz, DMSO-d6):
d 163.24, 162.19,
161.90, 158.76, 155.24, 149.22, 136.84, 134.64, 131.51, 130.32, 128.41,
127.84, 127.65, 118.36, 116.46, 111.37, 94.77, 69.30, 48.28, 35.14,
27.91, 20.27, 15.04. HPLC purity: 99.0%, tR ¼ 6.222 min. HRMS (ESI):
calcd for [C26H29N5OS þ H]þ 460.2166, found 460.2201.
5.2.16. N4-((2-(3-chlorophenyl)-4-methyl-5-thiazolyl)methyl)-N2-
isobutylpyrimidine-2,4-diamine (9b)
Compound 9b (83% yield) was prepared according to the
method described for the preparation of compound 9a except using
3-chlorobenzonitrile instead of 2-chlorobenzonitrile. 1H NMR
5.2.20. N4-((2-(4-(benzyloxy)phenyl)-4-methyl-5-thiazolyl)
methyl)-N2-isobutylpyrimidine-2,4-diamine (9f)
Compound 9f (82% yield) was prepared according to the method
described for the preparation of compound 9a except using 4-
(benzyloxy)benzonitrile instead of 2-chlorobenzonitrile. 1H NMR
(500 MHz, CDCl3)
d
7.87 (s, 1H, H-20 AreH), 7.70 (d, J ¼ 7.2 Hz,1H, H-
60 AreH), 7.59 (br s,1H, H-6 pyrimidine), 7.37e7.31 (m, 2H, H-40 and
H-50 AreH), 5.89 (s, 1H, H-5 pyrimidine), 4.72 (d, J ¼ 4.0 Hz, 2H,
CH2), 3.27 (t, J ¼ 6.2 Hz, 2H, CH2CH(CH3)2), 2.49 (s, 3H, CH3),
(500 MHz, DMSO)
d
7.66 (d, J ¼ 5.6 Hz, 1H, H-6 pyrimidine), 7.47 (d,
1.93e1.86 (m, 1H, CH(CH3)2), 0.98 (d, J ¼ 6.7 Hz, 6H, CH(CH3)2). 13
C
J ¼ 7.3 Hz, 2H, H-20 and H-60 AreH), 7.41e7.38 (m, 5H, OCH2AreH),
7.35e7.32 (m, 1H, H-30 or H-50 AreH), 7.09 (d, J ¼ 8.0 Hz, 1H, H-30 or
H-50 AreH), 5.75 (d, J ¼ 5.8 Hz, 1H, H-5 pyrimidine), 5.16 (s, 2H,
OCH2Ar), 4.61 (s, 2H, CH2), 3.09e3.08 (m, 2H, CH2CH(CH3)2), 2.42 (s,
3H, CH3), 1.86e1.81 (m, 1H, CH(CH3)2), 0.86 (d, J ¼ 6.7 Hz, 6H,
NMR (125 MHz, DMSO-d6):
d 161.96, 161.91, 150.13, 135.00, 133.89,
133.86, 131.15, 131.11, 129.58, 124.92, 124.85, 124.41, 96.00, 47.98,
35.35, 27.84, 20.08, 15.02. HPLC purity: 98.0%, tR ¼ 6.258 min. HRMS
(ESI): calcd for [C19H22ClN5S þ H]þ 388.1357, found 388.1394.
CH(CH3)2). 13C NMR (125 MHz, DMSO-d6):
d 163.53, 161.90, 159.66,
5.2.17. N4-((2-(4-chlorophenyl)-4-methyl-5-thiazolyl)methyl)-N2-
isobutylpyrimidine-2,4-diamine (9c)
158.00, 149.09, 137.37, 136.72, 129.73, 128.45, 127.92, 127.74, 127.19,
126.30, 115.30, 99.51, 69.37, 48.20, 35.12, 27.87, 20.23, 15.02. HPLC
Compound 9c (86% yield) was prepared according to the
method described for the preparation of compound 9a except using
4-chlorobenzonitrile instead of 2-chlorobenzonitrile. 1H NMR
purity: 96.1%, tR
¼
6.653 min. HRMS (ESI): calcd for
[C26H29N5OS þ H]þ 460.2166, found 460.2204.
(500 MHz, DMSO-d6)
d
7.85 (d, J ¼ 8.5, 2H, H-20 and H-60 AreH),
5.2.21. N4-((2-(4-fluorophenyl)-4-methyl-5-thiazolyl)methyl)-N2-
isobutylpyrimidine-2,4-diamine (9g)
Compound 9g (78% yield) was prepared according to the
method described for the preparation of compound 9a except using
7.66 (d, J ¼ 5.1 Hz, 1H, H-6 pyrimidine), 7.52 (d, J ¼ 8.5, 2H, H-30 and
H-50 AreH), 7.04 (br s, 1H, NH-4), 6.51 (br s, 1H, NH-2), 5.71 (d,
J ¼ 5.6 Hz, 1H, H-5 pyrimidine), 4.60 (d, J ¼ 5.2 Hz, 2H, CH2), 3.06 (t,