1016 Journal of Medicinal Chemistry, 2011, Vol. 54, No. 4
Gallardo-Godoy et al.
[4-(3,4-Dimethoxyphenyl)-thiazol-2-yl]-(4-methylpyridin-2-yl)-
amine (16). Intermediate 53 was reacted with commercially
available 2-bromo-1-(3,4-dimethoxyphenyl)-ethanone accord-
ing to the general procedure to afford the title compound in 68%
yield; mp 211-213 °C. 1H NMR (DMSO-d6) δ 11.46 (br s, 1H,
NH), 8.19 (d, J = 5.49 Hz, 1H), 7.48 (s, 1H), 7.46 (d, J = 2.01
Hz, 1H), 7.33 (s, 1H), 6.99 (d, J = 8.24 Hz, 1H), 6.93 (s, 1H), 6.83
(d, J = 4.94 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 3H), 2.31 (s, 3H).
LCMS (ESI) m/z 328 (MHþ).
[4-(3,4-Dimethoxyphenyl)-thiazol-2-yl]-isoquinolin-3-yl-amine
(17). Intermediate 59 was reacted with commercially available
2-bromo-1-(3,4-dimethoxyphenyl)-ethanone according to the
general procedure to afford the title compound in 78% yield;
mp 200-203 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.40 (s, 1H,
NH), 9.19 (s, 1H), 8.03 (d, J = 8.24 Hz, 1H), 7.80 (d, J = 8.06
Hz, 1H), 7.65 (td, J = 1.19, 7.55 Hz, 1H), 7.47-7.55 (m, 3H),
7.39-7.45 (m, 1H), 7.29 (s, 1H), 7.01 (d, J = 8.24 Hz, 1H), 3.84
(s, 3H), 3.79 (s, 3H). 13C NMR (100 MHz, chloroform-d) δ
161.4, 150.1, 149.6, 149.0, 148.7, 148.4, 138.3, 130.6, 128.6,
127.8, 125.7, 124.7, 124.3, 118.6, 111.4, 109.6, 103.1, 103.0,
56.0, 56.0. LCMS (ESI) m/z 364 (MHþ).
(5-Methylpyridin-2-yl)-[4-pyridin-4-yl)-thiazol-2-yl]-amine (23).
Intermediate 52 was reacted with commercially available 2-bro-
mo-1-pyridin-4-yl-ethanone according to the general procedure
to afford the title compound in 72% yield; mp decomposition at
291 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.58 (br s, 1H, NH),
8.90-8.95 (m, 2H), 8.42-8.46 (m, 2H), 8.40 (s, 1H), 8.16-8.20
(m, 1H), 7.62 (dd, J = 2.38, 8.42 Hz, 1H), 7.07 (d, J = 8.24 Hz,
1H), 2.25 (s, 3H). LCMS (ESI) m/z 269 (MHþ).
(5-Methylpyridin-2-yl)-(4-pyridin-2-yl-thiazol-2-yl)-amine (24).
Intermediate 52 was reacted with commercially available 2-bro-
mo-1-pyridin-2-yl-ethanone according to the general procedure
to afford the title compound in 62% yield; mp 184-190 °C. 1H
NMR (400 MHz, DMSO-d6) δ 11.31 (s, 1H, NH), 8.59 (dt, J =
0.92, 4.76 Hz, 1H), 8.13-8.17 (m, 1H), 7.93-7.98 (m, 1H), 7.87
(td, J = 1.28, 7.69 Hz, 1H), 7.61 (s, 1H), 7.56 (dd, J = 2.20, 8.42
Hz, 1H), 7.27-7.34 (m, 1H), 7.03 (d, J = 8.42 Hz, 1H), 2.23 (s,
3H). LCMS (ESI) m/z 269 (MHþ).
(5-Methylpyridin-2-yl)-(4-phenylthiazol-2-yl)-amine (25). In-
termediate 52 was reacted with commercially available 2-bro-
mo-1-phenyl-ethanone according to the general procedure to
1
afford the title compound in 82% yield; mp 260-264 °C. H
[4-(3,4-Dimethoxyphenyl)-thiazol-2-yl]-quinolin-2-yl-amine (18).
Intermediate 60 was reacted with commercially available 2-bro-
mo-1-(3,4-dimethoxyphenyl)-ethanone according to the general
procedure to afford the title compound in 80% yield; mp
NMR (400 MHz, methanol-d4) δ 8.32-8.37 (m, 1H), 8.17 (dd,
J = 2.01, 8.97 Hz, 1H), 7.93-8.01 (m, 2H), 7.54 (s, 1H), 7.45-
7.52 (m, 2H), 7.33-7.45 (m, 2H), 2.43 (s, 3H). LCMS (ESI) m/z
268 (MHþ).
1
257-259 °C. H NMR (400 MHz, DMSO-d6) δ 11.82 (br s,
(5-Methylpyridin-2-yl)-[4-(5-pyridin-2-yl-thiophen-2-yl)-thia-
zol-2-yl]-amine (26). Intermediate 52 was reacted with commer-
cially available 2-bromo-1-(5-pyridin-2-yl-thiophen-2-yl)-
ethanone according to the general procedure to afford the title
compound in 73% yield; mp 197-199 °C. 1H NMR (400 MHz,
DMSO-d6) δ 11.37 (s, 1H, NH), 8.52 (d, J = 5.86 Hz, 1H), 8.13
(s, 1H), 7.88-7.92 (m, 1H), 7.77-7.86 (m, 1H), 7.73-7.77 (m,
1H), 7.55 (dd, J = 2.20, 8.42 Hz, 1H), 7.50 (d, J = 3.85 Hz, 1H),
7.33 (s, 1H), 7.25 (dd, J = 4.76, 7.33 Hz, 1H), 7.02 (d, J = 8.42
Hz, 1H), 2.22 (s, 3H). LCMS (ESI) m/z 351 (MHþ).
(5-Methylpyridin-2-yl)-[4-(3-phenylisoxazol-5-yl)-thiazol-2-yl]-
amine (27). Intermediate 52 was reacted with commercially
available 2-bromo-1-(3-phenylisoxazol-5-yl)-ethanone accord-
ing to the general procedure to afford the title compound in 63%
yield; mp 224-227 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.56
(s, 1H, NH), 8.17 (s, 1H), 7.88-7.99 (m, 2H), 7.65 (s, 1H), 7.51-
7.61 (m, 4H), 7.19 (s, 1H), 7.02 (d, J = 8.42 Hz, 1H), 2.24 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 166.9, 162.9, 161.3, 150.1,
146.4, 139.7, 137.9, 131.0, 129.8 (2), 129.2, 127.4 (2), 125.8,
112.1, 111.2, 99.0, 17.9. LCMS (ESI) m/z 335 (MHþ).
1H, NH), 8.23 (d, J = 8.97 Hz, 1H), 7.83-7.88 (m, 2H), 7.69 (td,
J = 1.37, 7.65 Hz, 1H), 7.47-7.53 (m, 2H), 7.44 (s, 1H),
7.39-7.44 (m, 1H), 7.28 (d, J = 8.79 Hz, 1H), 7.02 (d, J =
8.24 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 159.7, 151.2, 149.5, 149.4, 149.1, 146.6, 138.5,
130.6, 128.6, 128.5, 126.6, 124.7, 124.4, 118.7, 113.5, 112.6,
110.0, 105.8, 56.2, 56.2. LCMS (ESI) m/z 364 (MHþ).
[4-(3,4-Dimethoxyphenyl)-thiazol-2-yl]-naphthalen-2-yl-amine
(19). Intermediate 64 was reacted with commercially available
2-bromo-1-(3,4-dimethoxyphenyl)-ethanone according to the
general procedure to afford the title compound in 68% yield;
mp 221-224 °C. 1H NMR (400 MHz, DMSO-d6) δ 10.49 (s, 1H,
NH), 8.54 (s, 1H), 7.87 (d, J = 8.97 Hz, 1H), 7.81 (t, J = 9.16 Hz,
2H), 7.53-7.61 (m, 3H), 7.47 (t, J = 7.42 Hz, 1H), 7.31-7.38
(m, 1H), 7.29 (s, 1H), 7.05 (d, J = 8.79 Hz, 1H), 3.89 (s, 3H), 3.81
(s, 3H). LCMS (ESI) m/z 363 (MHþ).
[4-(3,4-Dimethoxyphenyl)-thiazol-2-yl]-naphthalen-1-yl-amine
(20). Naphthalen-1-yl-thiourea (TCI America) was reacted with
commercially available 2-bromo-1-(3,4-dimethoxyphenyl)-
ethanone according to the general procedure to afford the title
compound in 59% yield; mp 244-246 °C. 1H NMR (400 MHz,
DMSO-d6) δ 10.24 (br s, 1H, NH), 8.27-8.33 (m, 1H), 8.23 (dd,
J = 2.93, 7.51 Hz, 1H), 7.96 (dt, J = 2.38, 4.76 Hz, 1H), 7.70 (d,
J = 8.06 Hz, 1H), 7.51-7.61 (m, 3H), 7.41-7.48 (m, 2H), 7.21
(s, 1H), 7.01 (d, J = 8.97 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 3H).
LCMS (ESI) m/z 363 (MHþ).
[4-(4-Methoxyphenyl)-thiazol-2-yl]-(5-methylpyridin-2-yl)-
amine (21). Intermediate 52 was reacted with commercially
available 2-bromo-1-(4-methoxyphenyl)-ethanone according
to the general procedure to afford the title compound in 73%
yield; mp 246-248 °C. 1H NMR (400 MHz, DMSO-d6) δ 11.60
(br s, 1H, NH), 8.21 (s, 1H), 7.79-7.94 (m, J = 8.61 Hz, 2H),
7.69 (br s, 1H), 7.32 (br s, 1H), 7.13 (br s, 1H), 6.97-7.04 (m, J =
7.87 Hz, 2H), 3.81 (s, 3H), 2.28 (s, 3H). LCMS (ESI) m/z 298
(MHþ).
[4-(2-Methoxyphenyl)-thiazol-2-yl]-(5-methylpyridin-2-yl)-
amine (22). Intermediate 52 was reacted with commercially
available 2-bromo-1-(2-methoxyphenyl)-ethanone according
to the general procedure to afford the title compound in 78%
yield; mp 228-230 °C. 1H NMR (400 MHz, methanol-d4) δ 8.34
(s, 1H), 8.00 (dd, J = 1.92, 8.70 Hz, 1H), 7.94 (d, J = 7.87 Hz,
1H), 7.62 (s, 1H), 7.40-7.49 (m, 1H), 7.25 (d, J = 8.79 Hz, 1H),
7.20 (d, J = 8.42 Hz, 1H), 7.08-7.16 (m, 1H), 4.02 (s, 3H), 2.41
(s, 3H). LCMS (ESI) m/z 298 (MHþ).
[4-(5-Methyl-3-phenylisoxazol-4-yl)-thiazol-2-yl]-(5-methyl-
pyridin-2-yl)-amine (28). Intermediate 52 was reacted with com-
mercially available 2-bromo-1-(5-methyl-3-phenylisoxazol-4-
yl)-ethanone according to the general procedure to afford the
1
title compound in 54% yield; mp 267-269 °C. H NMR (400
MHz, methanol-d4) δ 8.12 (dd, J = 2.11, 8.88 Hz, 1H), 7.71 (s,
1H), 7.51-7.57 (m, 2H), 7.40-7.48 (m, 3H), 7.31 (d, J = 8.97
Hz, 1H), 7.22 (s, 1H), 2.64 (s, 3H), 2.37 (s, 3H). LCMS (ESI) m/z
349 (MHþ).
(5-Methylpyridin-2-yl)-(4-methylthiazol-2-yl)-amine (29). In-
termediate 52 was reacted with commercially available 1-bro-
mo-propan-2-one according to the general procedure to afford
the title compound in 64% yield; mp 212-214 °C. 1H NMR (400
MHz, DMSO-d6) δ d 11.01 (br s, 1H, NH), 8.09 (s, 1H), 7.51 (dd,
J = 2.01, 8.42 Hz, 1H), 6.94 (d, J = 8.42 Hz, 1H), 6.48 (s, 1H),
2.21 (s, 3H), 2.20 (s, 3H). LCMS (ESI) m/z 206 (MHþ).
Isoquinolin-3-yl-[4-(4-methoxyphenyl)-thiazol-2-yl]-amine (30).
Intermediate 59 was reacted with commercially available 2-bromo-
1-(4-methoxyphenyl)-ethanone according to the general proce-
dure to afford the title compound in 57% yield; mp 224-228 °C.
1H NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H, NH), 9.19 (s,
1H), 8.02 (d, J = 8.06 Hz, 1H), 7.84-7.92 (m, 2H), 7.81 (d, J =
8.24 Hz, 1H), 7.61-7.71 (m, 1H), 7.54 (br s, 1H), 7.38-7.47 (m,
1H), 7.19-7.28 (m, 1H), 6.93-7.05 (m, 2H), 3.79 (s, 3H). LCMS
(ESI) m/z 334 (MHþ).