Page 13 of 19
Journal of Medicinal Chemistry
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NMR (151 MHz, CDCl3) δ ppm 163.8, 161.4, 146.2,
6.2 Hz, 6 H). 13C NMR (151 MHz, (CD3)2CO) δ ppm
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138.7, 129.4, 128.1, 119.6, 112.9, 71.7, 66.4, 37.7,
29.7, 22.1. HRMS (ESI‐TOF) calcd for C16H21ClN3O2S
[M+H]+: 354.1037, found 354.1040.
154.5, 151.7, 138.0, 130.9, 127.3, 120.3, 117.4,
111.0, 107.7, 103.4, 62.2, 56.9, 28.0, 21.1, 12.6, 10.5.
HRMS (ESI‐TOF) calcd for C17H23ClN3O2S: 368.1194,
found 368.1194 [M+H]+.
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2‐((4‐Chlorophenyl)amino)‐N‐(3‐ethoxypro‐
pyl) thiazole‐4‐carboxamide (18). Scheme 1,
general procedure D, using 2‐((4‐chloro‐
phenyl)amino)thiazole‐4‐carboxylic acid and 3‐
2‐((4‐Chloro‐3‐methylphenyl)amino)‐N‐(3‐
ethoxypropyl)thiazole‐4‐carboxamide(21).
Scheme 1, general procedure I, using 2‐chloro‐N‐(3‐
ethoxypropylamine.
Orange solid, 49% yield
ethoxypropyl)thiazole‐4‐carboxamide
and
4‐
(126.2 mg). Rf = 0.21 (5% MeOH in DCM). m.p.
chloro‐3‐methylaniline. Orange solid, 33% yield
o
138.2‐142.5 C. 1H NMR (600 MHz, (CD3)2CO) δ
(91.8 mg). Rf = 0.53 (5% MeOH in DCM). m.p.
o
ppm 9.62 (br. s, 1 H), 7.84 (br. s, 1 H), 7.76 (m, 2 H),
7.47 (s, 1 H), 7.30 (m, 2 H), 3.50 (t, J = 6.0 Hz, 2 H),
3.46 (m, 4 H), 1.83 (quint, J = 6.5 Hz, 2 H), 1.13 (t, J
= 6.9 Hz, 3 H). 13C NMR (151 MHz, (CD3)2SO) δ ppm
162.7, 160.5, 146.1, 139.7, 128.7, 124.7, 118.7,
113.2, 67.9, 65.4, 36.6, 29.6, 15.1. HRMS (ESI‐TOF)
calcd for C15H19ClN3O2S: 340.0881, found 340.0881
[M+H]+.
108.8‐112.6 C. 1H NMR (500 MHz, (CD3)2CO) δ
ppm 9.55 (br. s, 1 H), 7.85 (m, 1 H), 7.65 (dd, J = 8.6,
2.4 Hz, 1 H), 7.59 (s, 1 H), 7.47 (s, 1 H), 7.27 (d, J =
8.7 Hz, 1 H), 3.51 (t, J = 6.2 Hz, 2 H), 3.46 (m, 4 H),
2.34 (s, 3 H), 1.84 (quint, J = 6.4 Hz, 2 H), 1.12 (t, J =
6.9 Hz, 3 H). 13C NMR (151 MHz, (CD3)2CO) δ ppm
164.4, 161.8, 147.8, 140.8, 137.2, 130.2, 127.3,
120.8, 117.6, 113.4, 69.4, 66.7, 38.0, 30.7, 20.4, 15.6.
HRMS (ESI‐TOF) calcd for C16H21ClN3O2S: 354.1037,
found 354.1038 [M+H]+.
2‐((4‐Chloro‐3‐methylphenyl)amino)‐N‐(3‐
morpholinopropyl)thiazole‐4‐carboxamide
(19). Scheme 1, general procedure I, using 2‐
chloro‐N‐(3‐morpholinopropyl)thiazole‐4‐carbox‐
amide and 4‐chloro‐3‐methylaniline. Red solid,
45% yield (99.2 mg). Rf = 0.38 (5% MeOH in DCM).
m.p. 67.8‐79.4 oC. 1H NMR (600 MHz, (CD3)2CO) δ
ppm 9.59 (br. s, 1 H), 7.92 (t, J = 5.3 Hz, 1 H), 7.65
(dd, J = 8.7, 2.6 Hz, 1 H), 7.56 (d, J = 2.3 Hz, 1 H), 7.49
(s, 1 H), 7.27 (d, J = 8.5 Hz, 1 H), 3.58 (m, 4 H), 3.45
(q, J = 6.7 Hz, 2 H), 2.39 (m, 6 H), 2.33 (s, 3 H), 1.77
(quin, J = 6.9 Hz, 2 H). 13C NMR (151 MHz, (CD3)2CO)
δ ppm 164.5, 161.9, 147.7, 140.8, 137.2, 130.2,
127.4, 120.9, 117.7, 113.6, 67.4, 57.5, 54.7, 38.6,
27.2, 20.4. HRMS (ESI‐TOF) calcd for C18H24ClN4O2S:
395.1303, found 395.1305 [M+H]+.
2‐((4‐Chloro‐3,5‐dimethylphenyl)amino)‐N‐
(3‐morpholinopropyl)thiazole‐4‐carboxamide
(22). Scheme 1, general procedure I, using 2‐
chloro‐N‐(3‐morpholinopropyl)thiazole‐4‐carbox‐
amide and 4‐chloro‐3,5‐dimethylaniline. Pale yel‐
low solid, 34% yield (79.5 mg). Rf = 0.19 (5% MeOH
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in DCM). m.p. 137.5‐142.3 oC. H NMR (600 MHz,
CDCl3) δ ppm 7.87 (m, 1 H), 7.53 (br. s, 1 H), 7.43 (s,
1 H), 7.10 (s, 2 H), 3.75 (m, 4 H), 3.52 (q, J = 6.3 Hz,
2 H), 2.47 (m, 6 H), 2.38 (s, 6 H), 1.78 (quint, J = 6.6,
2 H). 13C NMR (151 MHz, CDCl3) δ ppm 164.6, 161.4,
146.1, 137.7, 137.4, 129.3, 118.8, 112.6, 66.8, 57.3,
53.7, 38.6, 26.8, 21.0. HRMS (ESI‐TOF) calcd for
C19H26ClN4O2S: 409.1459, found 409.1458 [M+H]+.
2‐((4‐Chloro‐3‐methylphenyl)amino)‐N‐(3‐
isopropoxypropyl)thiazole‐4‐carboxamide
(20). Scheme 1, general procedure I, using 2‐
chloro‐N‐(3‐isopropoxypropyl)thiazole‐4‐carbox‐
amide and 4‐chloro‐3‐methylaniline. Orange solid,
33% yield (95.4 mg). Rf = 0.49 (5% MeOH in DCM).
2‐((4‐Chloro‐3,5‐dimethylphenyl)amino)‐N‐
(3‐isopropoxypropyl)thiazole‐4‐carboxamide
(23). Scheme 1, general procedure I, using 2‐
chloro‐N‐(3‐isopropoxypropyl)thiazole‐4‐carbox‐
amide and 4‐chloro‐3,5‐dimethylaniline. Pale yel‐
low solid, 51% yield (93.0 mg). Rf = 0.28 (5% MeOH
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m.p. 127.0‐130.9 oC. H NMR (600 MHz, (CD3)2CO)
in DCM). m.p. 147.7‐151.0 oC. H NMR (500 MHz,
δ ppm 9.48 (br. s, 1 H), 7.79 (t, J = 5.1 Hz, 1 H), 7.64
(dd, J = 8.7, 2.6 Hz, 1 H), 7.59 (d, J = 2.3 Hz, 1 H), 7.46
(s, 1 H), 7.27 (d, J = 8.7 Hz, 1 H), 3.55 (spt, J = 6.2 Hz,
1 H), 3.51 (t, J = 6.0 Hz, 2 H), 3.46 (q, J = 6.7 Hz, 2 H),
2.34 (s, 3 H), 1.82 (quint, J = 6.4 Hz, 2 H), 1.09 (d, J =
(CD3)2CO) δ ppm 9.35 (br. s, 1 H), 7.74 (m, 1 H), 7.49
(s, 2 H), 7.44 (s, 1 H), 3.55 (m, 3 H), 3.46 (q, J = 6.7
Hz, 2 H), 2.35 (s, 6 H), 1.83 (quint, J = 6.4 Hz, 2 H),
1.09 (d, J = 6.2 Hz, 6 H). 13C NMR (151 MHz,
(CD3)2CO) δ ppm 164.5, 161.7, 147.9, 140.1, 137.5,
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