60
H. Kaur et al. / European Journal of Medicinal Chemistry 101 (2015) 52e62
(dichloromethane/hexane). IR (KBr): nmax 1578, 2213, 2927, 3060,
3282 cmꢀ1. 1H NMR (300 MHz, CDCl3, 25 ꢂC):
1.87e1.92 (m, 4H,
5.4.6. 2-Methylthio-4-(p-nitrophenyl)-6-[(7-chloroquinolin-4-yl)
aminobutyl]aminopyrimidine-5-carbonitrile (13f)
d
2 ꢃ CH2), 2.56 (s, 3H, SCH3), 3.42e3.45 (m, 2H, CH2), 3.60e3.69 (m,
2H, CH2), 5.03 (br, 1H, D2O exchangeable, NH), 5.74 (br, 1H, D2O
exchangeable, NH), 6.44 (d, 1H, J 5.1 Hz, ArH), 7.36 (d, 1H, J 2.1 Hz,
ArH), 7.39e7.53 (m, 3H, ArH), 7.68 (d, 1H, J 9.0 Hz, ArH), 7.95e7.97
(m, 3H, ArH), 8.55 (d, 1H, J 5.4 Hz, ArH). 13C NMR (75 MHz, CDCl3,
Chromatograpic eluent: ethyl acetate/hexane (90:10 v/v). Yellow
solid. Rf: 0.45 (ethyl acetate). Yield: 88%. m.p. 150e152 ꢂC
(dichloromethane/hexane). IR (KBr): nmax 1351, 1547, 1580, 2208,
2927, 3065, 3335 cmꢀ1
.
1H NMR (300 MHz, CDCl3, 25 ꢂC):
d
1.86e1.91 (m, 4H, 2 ꢃ CH2), 2.57 (s, 3H, SCH3), 3.42e3.44 (m, 2H,
25 ꢂC):
d
14.0, 25.5, 26.5, 41.0, 42.5, 79.6, 83.3, 99.1, 116.7, 117.9,
CH2), 3.71e3.73 (m, 2H, CH2), 6.43 (d,1H, J 5.4 Hz, ArH), 7.37 (dd,1H,
J 2.4 Hz, 9.0 Hz, ArH), 7.68 (d, 1H, J 2.4 Hz, ArH), 7.96 (d, 1H, J 2.1 Hz,
ArH), 8.10 (dd, 2H, J 1.8 Hz, 9.0 Hz, ArH), 8.35 (dd, 2H, J 1.8 Hz,
6.0 Hz, ArH), 8.53 (d, 1H, J 5.4 Hz, ArH). 13C NMR (75 MHz, CDCl3,
124.4, 124.5, 127.9, 128.9, 131.4, 133.8, 136.4, 149.5, 150.5, 152.3,
161.5, 167.3 and 174.4. Anal. Calcd. for C25H23ClN6S: C, 63.29; H,
4.85; N, 17.72; S, 6.75. Found: C, 63.14; H, 4.72; N, 17.64; S, 6.67.
EIMS: m/z 475 (M þ H)þ. UV/vis (CH2Cl2): lmax (ε/L molꢀ1 cmꢀ1
)
25 ꢂC):
d 13.6, 24.9, 25.9, 40.5, 42.0, 98.3, 101.5, 117.4, 123.3, 123.8,
252 nm (23710), 324 nm (7210).
127.1, 129.8, 133.5, 141.8, 148.5, 150.2, 151.3, 160.8 and 174.3. Anal.
Calcd. for C25H22ClN7O2S: C, 57.80; H, 4.23; N, 18.88, S, 6.16; Found:
C, 57.68; H, 4.23; N, 18.89; S 6.27. EIMS: m/z 520 (M þ H)þ. UV/vis
(CH2Cl2): lmax (ε/L molꢀ1 cmꢀ1) 252 nm (19840), 320 nm (4630).
5.4.3. 2-Methylthio-4-phenyl-6-[(7-chloroquinolin-4-yl)
aminopropoxy]pyrimidine-5-carbonitrile (13c)
Chromatograpic eluent: ethyl acetate/methanol (99:1 v/v).
White solid. Rf: 0.50 (ethyl acetate). Yield: 89%. m.p. 138e140 ꢂC
(dichloromethane/hexane). IR (KBr): nmax 1332, 1580, 2220, 3061,
5.4.7. 2-Methylthio-4-(p-nitrophenyl)-6-[1-(7-chloroquinolin-4-yl]
piperazin-4-ylpyrimidine-5-carbonitrile (13g)
3212 cmꢀ1.1H NMR (300 MHz, CDCl3, 25 ꢂC):
d
2.29e2.33 (m, 2H,
Chromatograpic eluent: ethyl acetate/hexane (80:20 v/v). White
CH2), 2.62 (s, 3H, SCH3), 3.59e3.62 (m, 2H, CH2), 4.72 (t, 2H, J 5.4 Hz,
CH2), 5.40 (br,1H, D2O exchangeable, NH), 6.49 (d,1H, J 5.1 Hz, ArH),
7.39 (dd, 1H, J 2.1 Hz, 9.0 Hz, ArH), 7.42e7.56 (m, 3H, ArH), 7.82 (d,
1H, J 9.0 Hz, ArH), 7.95 (d, 1H, J 1.8 Hz, ArH), 8.06e8.03 (m, 2H, ArH),
solid. Rf: 0.54 (ethyl acetate). Yield: 91%. m.p. 190 ꢂC (dichloro-
methane/hexane). IR (KBr): nmax 1423,1533, 2210, 2923, 3039 cmꢀ1
.
1H NMR (300 MHz, CDCl3, 25 ꢂC):
d 2.59 (s, 3H, SCH3), 3.50e3.52 (m,
4H, 2 ꢃ CH2), 4.30e4.33 (m, 4H, 2 ꢃ CH2), 6.92 (d, 1H, J 5.4 Hz, ArH),
8.55 (d, 1H, J 5.7 Hz, ArH). 13C NMR (75 MHz, CDCl3, 25 ꢂC):
d 14.4,
7.52 (dd, 1H, J 2.0 Hz, 9.0 Hz, ArH), 7.98e8.07 (m, 3H, ArH), 8.19 (s,
27.7, 40.2, 66.5, 100.1, 115.4, 116.3, 121.3, 125.6, 128.8, 128.9, 131.9,
135.2, 148.4, 150.3, 152.6, 165.3, 168.5 and 173.2. Anal. Calcd. for
1H, ArH), 8.35 (d, 2H, J 9.0 Hz, ArH), 8.75 (d, 1H, J 5.1 Hz, ArH). 13
C
NMR (75 MHz, CDCl3, 25 ꢂC):
d 13.5, 14.1, 29.5, 29.7, 46.9, 51.6, 123.4,
C
24H20ClN5OS: C, 62.47; H, 4.33; N,15.18; S, 6.94. Found: C, 62.54; H,
126.9, 130.3 and 152.2. Anal. Calcd. for C25H20ClN7O2S: C, 58.02; H,
3.86; N, 18.95; S, 6.19. Found: C, 57.91; H, 4.00; N, 18.90; S, 6.19.
4.31; N, 15.11; S, 6.90. EIMS: m/z 462 (M þ H)þ. UV/vis (CH2Cl2):
lmax (ε/L molꢀ1 cmꢀ1) 252 nm (10780), 312 nm (3280).
EIMS: m/z 518 (M þ H)þ. UV/vis (CH2Cl2): lmax (ε/L molꢀ1 cmꢀ1
)
252 nm (15690), 323 nm sh (4678).
5.4.4. 2-Methylthio-4-phenyl-6-[1-(7-chloroquinolin-4-yl]
piperazin-4-yl]pyrimidine-5-carbonitrile (13d)
5.4.8. 2-Methylthio-4-(p-methoxylphenyl)-6-[(7-chloroquinolin-4-
Chromatograpic eluent: ethyl acetate/hexane (80:20 v/v).White
solid. Rf: 0.87 (ethyl acetate). Yield: 85%. m.p. 188e190 ꢂC
(dichloromethane/hexane). IR (KBr): nmax 1578, 2206, 2822, 2924,
yl)aminobutyl]aminopyrimidine-5-carbonitrile (13h)
Chromatograpic eluent: ethyl acetate/hexane (80:20 v/v). Yellow
solid. Rf: 0.46 (ethyl acetate). Yield: 80%. m.p. 145e147 ꢂC
(dichloromethane/hexane). IR (KBr): nmax 1050, 1259, 1566, 2210,
3035 cmꢀ1. 1H NMR (300 MHz, CDCl3, 25 ꢂC):
d 2.59 (s, 3H, SCH3),
3.38 (t, 4H, J 4.8 Hz, 2 ꢃ CH2), 4.27 (t, 4H, J 4.8 Hz, 2 ꢃ CH2), 6.88 (d,
1H, J 4.8 Hz, ArH), 7.46e7.57 (m, 4H, ArH), 7.89 (dd, 2H, J 1.5 Hz,
6.3 Hz, ArH), 7.98 (d, 1H, J 9.0 Hz, ArH), 8.08 (d, 1H, J 2.1 Hz, ArH),
2948, 3309 cmꢀ1. 1H NMR (300 MHz, CDCl3, 25 ꢂC):
d 1.77e1.79 (m,
4H, 2 ꢃ CH2), 2.48 (s, 3H, SCH3), 3.30e3.33 (m, 2H, CH2), 3.60e3.62
(m, 2H, CH2), 3.80 (s, 3H, OCH3), 5.00 (br, 1H, D2O exchangeable,
NH), 5.70 (br, 1H, D2O exchangeable, NH), 6.36 (d, 1H, J 5.4 Hz, ArH),
6.93 (d, 2H, J 9.0 Hz, ArH), 7.30 (d, 1H, J 7.2 Hz, ArH), 7.60 (d, 1H, J
8.76 (d, 1H, J 4.8 Hz, ArH). 13C NMR (75 MHz, CDCl3, 25 ꢂC):
d 14.4,
47.2, 51.9, 84.1, 109.3, 118.3, 124.7, 126.6, 128.5, 129.0, 129.3, 131.4,
135.2,136.1,150.1,151.9,156.1,162.9,170.8 and 174.5. Anal. Calcd. for
8.7 Hz, ArH), 7.95e7.89 (m, 3H, ArH), 8.47 (d, 1H, J 5.1 Hz, ArH). 13
C
C
25H21ClN6S: C, 63.55; H, 4.44; N, 17.79; S, 6.77. Found: C, 63.61; H,
NMR (75 MHz, CDCl3, 25 ꢂC):
116.4, 123.3, 127.9, 131.2, 132.9 and 154.4. Anal. Calcd. for
d 16.7, 28.4, 29.4, 32.1, 45.1, 57.9, 101.5,
4.34; N, 17.71; S, 6.70. EIMS: m/z 473 (M þ H)þ. UV/vis (CH2Cl2):
lmax (ε/L molꢀ1 cmꢀ1) 252 nm (14890), 329 nm sh (2330).
C
26H25ClN6OS: C, 61.90; H, 4.96; N, 16.66, S, 6.34. Found: C, 61.74; H,
5.03; N, 16.71; S, 6.43. EIMS: m/z 505 (M þ H)þ. UV/vis (CH2Cl2):
5.4.5. 2-Methylthio-4-(m-nitrophenyl)-6-[(7-chloroquinolin-4-yl)
aminobutyl]aminopyrimidine-5-carbonitrile (13e)
lmax (ε/L molꢀ1 cmꢀ1) 252 nm (13940), 310 nm (7140).
Chromatograpic eluent: ethyl acetate/hexane (90:10 v/v).Yellow
solid. Rf: 0. 34 (ethyl acetate). Yield: 84%. m.p. 155e157 ꢂC
(dichloromethane/hexane). IR (KBr): nmax 1347, 1583, 1725, 2202,
5.4.9. 2-Methylthio-4-(3,4-dimethoxylphenyl)-6-[(7-
chloroquinolin-4-yl)aminobutyl] aminopyrimidine-5-carbonitrile
(13i)
3056, 3360 cmꢀ1. 1H NMR (300 MHz, CDCl3, 25 ꢂC):
d
1.86e1.88 (m,
Chromatograpic eluent: ethyl acetate/hexane (85:15 v/v). Yellow
solid. Rf: 0.39 (ethyl acetate). Yield: 85%. m.p. 108 ꢂC (dichloro-
methane/hexane). IR (KBr): nmax 1022,1262,1489,1581, 2202, 2963,
4H, 2 ꢃ CH2), 2.69 (s, 3H, SCH3), 3.40e3.43 (m, 2H, CH2), 3.70e3.72
(m, 2H, CH2), 5.01 (br, 1H, D2O exchangeable, NH), 5.82 (br, 1H, D2O
exchangeable, NH), 6.44 (d, 1H, J 5.7 Hz, ArH), 7.38 (dd, 1H, J 2.1 Hz,
4.5 Hz, ArH), 7.69 (dd, 1H, J 7.1 Hz, 13.8 Hz, ArH), 7.96 (d, 1H, J 2.1 Hz,
ArH), 8.29 (d, 1H, J 7.1 Hz, ArH), 8.38 (d, 2H, J 7.2 Hz, ArH), 8.55 (d,
1H, J 5.4 Hz, ArH), 8.82 (s, 1H, ArH). 13C NMR (75 MHz, CDCl3, 25 ꢂC):
3351 cmꢀ1. 1H NMR (300 MHz, CDCl3, 25 ꢂC):
d 1.72e1.75 (m, 4H,
2 ꢃ CH2), 2.45 (s, 3H, SCH3), 3.29e3.31 (m, 2H, CH2), 3.57e3.59 (m,
2H, CH2), 3.84 (d, 6H, J 3.0 Hz, 2 ꢃ OCH3), 5.05 (br, 1H, D2O
exchangeable, NH), 5.70 (br,1H, D2O exchangeable, NH), 6.31 (d,1H,
J 5.4 Hz, ArH), 6.85 (d, 1H, J 8.4 Hz, ArH), 7.26 (t, 1H, J 6.9 Hz, ArH),
7.47 (d, 1H, J 2.1 Hz, ArH), 7.57e7.60 (m, 2H, ArH), 7.85 (d, 1H, J
2.1 Hz, ArH), 8.41 (d, 1H, J 5.1 Hz, ArH). 13C NMR (75 MHz, CDCl3,
d
13.6, 24.9, 25.9, 40.5, 42.1, 83.0, 96.9, 98.5, 115.6, 117.3, 123.1, 123.7,
123.8, 125.1, 127.1, 129.8, 133.6, 134.4, 137.4, 147.6, 150.2, 151.3, 160.8,
164.2 and 174.3. Anal. Calcd. for C25H22ClN7O2S: C, 57.80; H, 4.23; N,
18.88, S, 6.16; Found: C, 57.68; H, 4.23; N, 18.89; S, 6.27 . EIMS: m/z
520 (M þ H)þ. UV/vis (CH2Cl2): lmax (ε/L molꢀ1 cmꢀ1) 252 nm
(15770), 326 nm (3350).
25 ꢂC):
121.3, 127.3, 147.1, 151.3, 160.3, 162.3 and 176.1. Anal. Calcd. for
27H27ClN6O2S: C, 60.67; H, 5.05; N, 15.73, S, 5.99. Found: C, 60.68;
d 13.1, 24.9, 26.3, 28.6, 40.4, 44.9, 55.0, 98.2, 110.4, 118.1,
C