CUARTAS ET AL.
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methanol and water to afford compounds 8a–g, which did not require
3 4
(93), and 43 (100). Anal. calcd. For C22H20Cl FN S: C, 53.08; H, 4.05;
further purification.
N, 11.25; S, 6.44. Found: C, 53.04; H, 4.02; N, 11.22; S, 6.49.
4
‐Chloro‐N,N‐bis(2‐chloroethyl)‐5‐[3‐(4‐chlorophenyl)‐1‐phenyl‐
,5‐dihydro‐1H‐pyrazol‐5‐yl]thiazol‐2‐amine (8a)
5‐[3‐(Benzo[d][1,3]dioxol‐5‐yl)‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐
5‐yl]‐4‐chloro‐N,N‐bis(2‐chloroethyl)thiazol‐2‐amine (8d)
4
−1
−1
Pale yellow solid; 66% yield; m.p. 146–148°C. FTIR (ATR) ν (cm ):
Pale yellow solid; 57% yield; m.p. 177–180°C. FTIR (ATR) ν (cm ):
3
,036 (═C–H), 2,958 and 2,914 (C–H), and 1,595 and 1,527 (C═N and
3,018 (═C–H), 2,961 and 2,910 (C–H), and 1,597 and 1,526 (C═N
1
1
C═C). H NMR (400 MHz, CDCl
3
) δ ppm 7.64 (d, J = 8.6 Hz, 2H, HBo),
and C═C). H NMR (400 MHz, CDCl
3
) δ ppm 7.40 (d, J = 1.4 Hz, 1H,
7
.36 (d, J = 8.6 Hz, 2H, HBm), 7.26 (t, J = 7.5 Hz, 2H, HCm), 7.16
d, J = 7.8 Hz, 2H, HCo), 6.88 (t, J = 7.3 Hz, 1H, HCp), 5.51 (dd, J = 11.8,
H
Bo′), 7.26 (t, J = 7.9 Hz, 2H, HCm), 7.16 (d, J = 7.9 Hz, 2H, HCo), 7.05
(dd, J = 8.1, 1.4 Hz, 1H, HBo), 6.90–6.80 (m, 2H, HBm, HCp), 6.00
(s, 2H, –OCH O–), 5.46 (dd, J = 11.6, 6.6 Hz, 1H, H5′), 3.81–3.73 (m,
5H, H4b′, 2×CH –N), 3.72–3.65 (m, 4H, 2×CH –Cl), and 3.15 (dd,
J = 17.0, 6.6 Hz, 1H, H4a′). C NMR (100 MHz, CDCl ) δ ppm 166.2
(
6
.6 Hz, 1H, H5′), 3.78–3.70 (m, 5H, H4b′, 2×CH
×CH –Cl), and 3.17 (dd, J = 17.1, 6.6 Hz, 1H, H4a′).
) δ ppm 166.2 (C), 146.7 (C), 144.5 (C), 134.9 (C),
32.3 (C), 130.9 (C), 129.3 (CH), 129.0 (CH), 127.2 (CH), 120.5 (CH),
19.3 (C), 114.1 (CH), 58.0 (C5′), 54.3 (CH ), 41.7 (C4′), and 40.7 (CH ).
2
–N), 3.70–3.65 (m, 4H,
2
1
3
2
2
C NMR
2
2
1
3
(100 MHz, CDCl
3
3
1
1
(C), 148.8 (C), 148.3 (C), 147.8 (C), 144.9 (C), 136.5 (C), 129.2 (CH),
126.8 (C), 120.6 (CH), 120.2 (CH), 119.7 (C), 114.0 (CH), 108.3 (CH),
2
2
+
+
+
+
MS (EI): m/z 512/514/516/518/520 [M /M + 2 /M + 4 /M + 6 /
106.0 (CH), 101.5 (–OCH
2
O–), 58.00 (C5′), 54.26 (CH
2
–N), 42.02
+
+
M + 8 ] (86/100/50/12/3), 477/479/481/483 (89/82/48/4), 274/276
(C4′), and 40.75 (CH
2
–Cl). MS (EI): m/z 522/524/526/528 [M /
+
+
+
(
49/21), and 173 (4). Anal. calcd. for C22
H
20Cl
4
N
4
S: C, 51.38; H, 3.92;
M + 2 /M + 4 /M + 6 ] (21/24/9/2), 487/489/491 (11/9/2), 91 (52),
57 (94), and 43 (100). Anal. calcd. for C23 21Cl S: C, 52.73; H,
.04; N, 10.69; S, 6.12. Found: C, 52.71; H, 4.07; N, 10.72; S, 6.09.
N, 10.89; S, 6.23. Found: C, 51.41; H, 3.91; N, 10.84; S, 6.28.
H
3 4 2
N O
4
5
4
‐[3‐(4‐Bromophenyl)‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐5‐yl]‐
‐chloro‐N,N‐bis(2‐chloroethyl)thiazol‐2‐amine (8b)
4‐Chloro‐N,N‐bis(2‐chloroethyl)‐5‐[3‐(4‐methoxyphenyl)‐1‐phenyl‐
4,5‐dihydro‐1H‐pyrazol‐5‐yl]thiazol‐2‐amine (8e)
−
1
Pale yellow solid; 60% yield; m.p. 132–133°C. FTIR (ATR) ν (cm ):
−1
3,038 (═C–H), 2,972 and 2,903 (C–H), and 1,593 and 1,535 (C═N
White solid; 50% yield; m.p. 150–152°C. FTIR (ATR) ν (cm ): 3,031
1
and C═C). H NMR (400 MHz, CDCl
3
) δ ppm 7.60 (d, J = 8.6 Hz, 2H,
(═C–H), 2,956 and 2,901 (C–H), and 1,595 and 1,533 (C═N and C═C).
1
H
Bo), 7.53 (d, J = 8.6 Hz, 2H, HBm), 7.29 (t, J = 7.4 Hz, 2H, HCm), 7.17 (d,
J = 8.1 Hz, 2H, HCo), 6.90 (t, J = 7.2 Hz, 1H, HCp), 5.53 (dd, J = 11.7,
H NMR (400 MHz, CDCl
Cm), 7.17 (d, J = 7.9 Hz, 2H,
(d, J = 8.8 Hz, 2H, HBm), 6.87 (t, J = 7.2 Hz, 1H, HCp), 5.46 (dd, J = 11.6,
6.7 Hz, 1H, H5′), 3.85 (s, 3H, OCH ), 3.80–3.72 (m, 5H, H4b′, 2×CH –N),
3.71–3.66 (m, 4H, 2×CH –Cl), and 3.19 (dd, J = 17.0, 6.7 Hz, 1H, H4a′).
C NMR (100 MHz, CDCl ) δ ppm 166.2 (C), 160.6 (C), 148.0 (C),
145.1 (C), 132.0 (C), 129.2 (CH), 127.6 (CH), 125.1 (C), 120.1 (CH),
3
) δ ppm 7.68 (d, J = 8.8 Hz, 2H, HBo), 7.27
(t, J = 7.6 Hz, 2H,
H
HCo), 6.94
6
.6 Hz, 1H, H5′), 3.83–3.72 (m, 5H, H4b′, 2×CH
×CH –Cl), and 3.19 (dd, J = 17.1, 6.6 Hz, 1H, H4a′).
) δ ppm 160.6 (C), 146.7 (C), 144.4 (C), 135.8 (C),
31.9 (CH), 131.3 (C), 129.3 (CH), 127.4 (CH), 124.8 (C), 120.5 (CH),
19.2 (s), 114.0 (CH), 58.0 (C5′), 54.3 (CH ), 41.6 (C4′), and 40.7
). MS (EI): m/z 556/558/560/562/564 [M /M + 2 /M + 4 /
2
–N), 3.72–3.63 (m, 4H,
1
3
2
2
C NMR
3
2
(
100 MHz, CDCl
3
2
13
1
1
3
2
+
+
+
(CH
2
3 2
119.9 (C), 114.2 (CH), 114.0 (CH), 57.9 (OCH ), 55.5 (C5′), 54.3 (CH ),
+
+
+
+
M + 6 /M + 8 ] (9/15/9/3/1), 521/523/525/527 (10/13/6/1), 97 (60),
and 57 (100). Anal. calcd. for C22 20BrCl S: C, 47.29; H, 3.61; N,
0.03; S, 5.74. Found: C, 47.32; H, 3.59; N, 10.01; S, 5.78.
42.0 (C4′), and 40.8 (CH
2
). MS (EI): m/z 508/510/512/514 [M /M + 2 /
+
+
H
N
3 4
M + 4 /M + 6 ] (27/35/12/3), 473/475/477 (14/8/1), 91 (72), 63 (100),
and 43 (81). Anal. calcd. for C23 23Cl OS: C, 54.18; H, 4.55; N,
0.99; S, 6.29. Found: C, 54.14; H, 4.57; N, 10.96; S, 6.31.
1
H
3 4
N
1
4
‐Chloro‐N,N‐bis(2‐chloroethyl)‐5‐[3‐(4‐fluorophenyl)‐1‐phenyl‐4,5‐
dihydro‐1H‐pyrazol‐5‐yl]thiazol‐2‐amine (8c)
Pale yellow solid; 61% yield; m.p. 134–136°C. FTIR (ATR) ν (cm ):
4‐Chloro‐N,N‐bis(2‐chloroethyl)‐5‐[1‐phenyl‐3‐(3,4,5‐
−
1
trimethoxyphenyl)‐4,5‐dihydro‐1H‐pyrazol‐5‐yl]thiazol‐2‐amine (8f)
−1
3,021 (═C–H), 2,961 and 2,935 (C–H), and 1,597 and 1,530 (C═N
White solid; 58% yield; m.p. 144–145°C. FTIR (ATR) ν (cm ): 3,032
1
and C═C). H NMR (400 MHz, CDCl
3
) δ ppm 7.72 (dd, J = 8.9,
(═C–H), 2,955 and 2,920 (C–H), and 1,591 and 1,530 (C═N and
4
1
J
H–F = 5.4 Hz, 2H,
HBo), 7.28 (t, J = 7.3 Hz, 2H,
HCm), 7.17
C═C). H NMR (400 MHz, CDCl
3
) δ ppm 7.29 (t, J = 7.3 Hz, 2H, HCm),
(
d, J = 7.7 Hz, 2H, HCo), 7.10 (t, J = 8.7 Hz, 2H, HBm), 6.89 (t, J = 7.3 Hz,
7.18 (d, J = 7.7 Hz, 2H, HCo), 6.97 (s, 2H, HBo), 6.89 (t, J = 7.3 Hz, 1H,
Cp), 5.51 (dd, J = 11.7, 6.6 Hz, 1H, H5′), 3.93 (s, 6H, 2×OCH ), 3.89
1
2
6
H, HCp), 5.50 (dd, J = 11.7, 6.7 Hz, 1H, H5′), 3.78–3.73 (m, 5H, H4b′
,
H
3
×CH –N), 3.72–3.67 (m, 4H, 2×CH –Cl), and 3.19 (dd, J = 17.1,
2
2
(s, 3H, OCH
CH
CDCl
132.1 (C), 129.3 (CH), 128.0 (C), 120.4 (CH), 119.6 (C), 114.0 (CH),
3
), 3.85–3.71 (m, 5H, H4b′, 2×CH
2
–N), 3.73–3.64 (m, 4H,
1
3
13
.7 Hz, 1H, H4a′). C NMR (100 MHz, CDCl
3
) δ ppm 166.2 (C), 163.3
2
–Cl), and 3.21 (dd, J = 17.0, 6.6 Hz, 1H, H4a′). C NMR (100 MHz,
1
(
d,
J
C–F = 232.5 Hz, C), 147.0 (C), 144.8 (C), 132.2 (C), 129.3 (CH),
3
) δ ppm 166.2 (C), 153.5 (C), 147.7 (C), 144.7 (C), 139.4 (C),
4
3
1
1
28.7 (d,
J
C–F = 3.0 Hz, C), 127.9 (d, JC–F = 8.3 Hz, CH), 120.4 (CH),
2
19.5 (C), 115.9 (d,
JC–F = 21.9 Hz, CH), 114.0 (CH), 58.1 (C5′), 54.3
103.4 (CH), 61.1 (OCH
(C4′), and 40.7 (CH
3
), 58.0 (C5′), 56.4 (OCH
3
), 54.3 (CH
2
), 42.0
+
+
+
(
CH
2
), 41.9 (C4′), and 40.7 (CH
2
). MS (EI): m/z 496/498/500/502 [M /
2
). MS (EI): m/z 568/570/572/574 [M /M + 2 /
+
+
+
+
+
M + 2 /M + 4 /M + 6 ] (6/6/1/1), 461/463/465 (5/3/1), 97 (44), 57
M + 4 /M + 6 ] (57/61/24/4), 533/535/537 (17/10/3), 91 (40), and 63