4
Tetrahedron
ACCEPTED MANUSCRIPT
4.2.10 4-methyl-5-(naphthalen-2-yl)thiazol-2-amine
(3j).
3H), 2.22 (s, 3H).13C NMR (125 MHz, DMSO-d6) δ 167.27,
1
Yield: 94%, light brown solid, mp:161.2-162.5°C; H NMR (500
MHz, CDCl3) δ 7.94 – 7.84 (m, 3H), 7.53 – 7.46 (m, 4H), 5.10 (s,
2H), 2.05 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 166.38, 145.40,
133.77, 132.89, 129.56, 129.47, 128.68, 128.35, 126.44, 126.04,
125.93, 125.24, 118.08, 15.71. HRMS (ESI): m/z calcd for
C14H13N2S [M+H]+: 241.0794, found: 241.0795.
144.88, 132.44, 130.95, 129.88, 129.15, 31.18, 16.96. HRMS
(ESI): m/z calcd for C11H12ClN2S [M+H]+: 239.0404, found:
239.0405.
4.2.19 5-(4-chlorophenyl)-4-methyl-N-phenylthiazol-2-amine
(3s) Yield: 82%, White solid, mp: 151.0-152.7°C; H NMR (500
1
MHz, CDCl3) δ 7.95 (s, 1H), 7.40 – 7.30 (m, 8H), 7.11 – 7.06 (m,
1H), 2.35 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 162.88, 143.88,
140.23, 132.77, 129.98, 129.55, 128.82, 123.34, 118.99, 118.67,
29.71, 16.21. HRMS (ESI): m/z calcd for C16H14ClN2S [M+H]+:
301.0561, found: 301.0563.
4.2.11 4-methyl-5-(pyridin-3-yl)thiazol-2-amine (3k). Yield:
87%, white solid, mp: 172.9-173.2; 1H NMR (500 MHz, DMSO-
d6) δ 8.55 (d, J = 1.8 Hz, 1H), 8.41 (dd, J = 4.7, 1.3 Hz, 1H), 7.75
– 7.71 (m, 1H), 7.39 (dd, J = 7.8, 4.8 Hz, 1H), 7.14 (s, 2H), 2.20
(s, 3H).13C NMR (125 MHz, DMSO-d6) δ 166.95, 148.68, 147.31,
145.44, 135.33, 129.81, 124.09, 114.06, 16.66. HRMS (ESI): m/z
calcd for C9H10N3S [M+H]+:192.0590, found: 192.0592.
Acknowledgements
This project was supported from the Zhejiang Provincial
Natural Science Foundation of China under Grant No.
LY16H300001, National Natural Science Foundation of China
(No. 81273356), National Science & Technology Major Projects
for "Major New Drugs Innovation and Development" of China
(2014ZX09304002-007), the Program for Zhejiang Leading
Team of S&T Innovation Team (2011R50014) and Arthritis &
Chronic Pain Research Institute, USA to Y. Yu.
4.2.12 4-methyl-5-propylthiazol-2-amine (3l). Yield: 77%, tan
liquid; H NMR (500 MHz, CDCl3) δ 4.95 (s, 2H), 2.51 (t, J =
7.4 Hz, 2H), 2.09 (s, 3H), 1.58 – 1.48 (m, 2H), 0.92 (t, J = 7.3 Hz,
3H).13C NMR (125 MHz, CDCl3) δ 164.34, 142.27, 121.32,
28.18, 24.85, 14.56, 13.52. HRMS (ESI): m/z calcd for C7H13N2S
[M+H]+: 157.0794, found: 157.0796.
1
4.2.13 N,4-dimethyl-5-phenylthiazol-2-amine (3m). Yield:
89%, white solid, mp: 149.9-150.9°C; 1H NMR (500 MHz,
CDCl3) δ 7.40 – 7.34 (m, 4H), 7.26 – 7.22 (m, 1H), 6.07 (s, 1H),
2.97 (s, 3H), 2.33 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 168.95,
143.80, 133.23, 128.61, 128.55, 126.46, 119.07, 32.11, 16.32.
HRMS (ESI): m/z calcd for C11H13N2S [M+H]+: 205.0794, found:
205.0795.
Supplementary data
Supplementary
data
(Experimental
procedures,
1
characterization data, and copies of H and 13C NMR spectra for
all products.) associated with this article can be found in online
4.2.14 4-methyl-N,5-diphenylthiazol-2-amine (3n). Yield: 85%,
1
white solid, mp: 148.5-149.4°C; H NMR (500 MHz, CDCl3) δ
References and notes
8.02 (s, 1H), 7.46 – 7.35 (m, 8H), 7.34 – 7.29 (m, 1H), 7.10 (m,
1H), 2.42 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 162.84, 143.35,
140.45, 132.62, 129.51, 128.83, 128.64, 126.91, 123.12, 120.25,
118.60, 16.25. HRMS (ESI): m/z calcd for C16H15N2S [M+H]+:
267.0950, found: 267.0953.
1
(a) Das, J.; Chen, P.; Norris, D.; Padmanabha, R.; Lin, J.;
Moquin, R. V.; Shen, Z.; Cook, L. S.; Doweyko, A. M.;
Pitt, S.; Pang, S.; Shen, D. R.; Fang, Q. J. Med. Chem.
2006
F.; Gokhale, V.; Dietrich, J.; Davis, A.; Meuillet, E.;
Hulme, C. Bioorg. Med. Chem. Lett. 2012 22, 3567-3570.
, 49, 6819-6832. (b) Smith, B.; Chang, H.-H.; Medda,
4.2.15 4-methyl-N-(4-nitrophenyl)-5-phenylthiazol-2-amine
1
(3o). Yield: 72%, yellow solid, mp: 217.7-218.5°C; H NMR
,
(500 MHz, DMSO-d6) δ 11.01 (s, 1H), 8.23 (d, J = 9.1 Hz, 2H),
7.85 (d, J = 9.0 Hz, 2H), 7.46 (t, J = 6.1 Hz, 4H), 7.35 (m, 1H),
2.39 (s, 3H). 13C NMR (125 MHz, DMSO-d6) δ 159.52, 147.25,
144.08, 140.63, 132.06, 129.39, 129.04, 127.78, 125.98, 122.20,
116.61, 16.83. HRMS (ESI): m/z calcd for C16H14N3O2S [M+H]+:
312.0801, found: 312.0806.
2
3
4
5
De Souza, M. V. N.; De Almeida M. V. Quim. Nova 2003
26, 366-372.
,
Pasqualotto, A. C.; Thiele, K. O.; Goldani, L. Z. Curr.
Opin. Investig. Drugs 2010 11,165-174.
,
Fox, L. M.; Saravolatz, L. D. Clin. Infect. Dis. 2005, 40,
1173-1180.
(a) Siddiqui, H. L.; Zia-ur-Rehman, M.; Ahmad, N.;
Weaver, G. W. Chem. Pharm. Bull. 2007, 55, 1014-1017.
(b) Franklin, P. X.; Pillai, A. D.; Rathod, P. D.; Yerande,
S. G.; Nivsarkar, M.; Padh, H.; Sudarsanam, V.; Vasu, K.
K. Eur. J. Med. Chem. 2008, 43, 129-134. (c) Inamdar, G.
S.; Pandya, A. N.; Thakar, H. M. V.; Sudarsanam,
Kachler, S.; Sabbadin, D.; Moro, S.; Klotz, K.-N.; Vasu,
4.2.16 N-(4-methoxyphenyl)-4-methyl-5-phenylthiazol-2-amine
1
(3p). Yield: 87%, white solid, mp: 121.6-123.5°C; H NMR (500
MHz, CDCl3) δ 7.84 (s, 1H), 7.39 – 7.33 (m, 4H), 7.32 – 7.27 (m,
2H), 7.27 – 7.23 (m, 2H), 6.94 – 6.89 (m, 2H), 3.81 (s, 3H), 2.34
(s, 3H). 13C NMR (125 MHz, CDCl3) δ 165.08, 156.58, 142.99,
133.60, 132.67, 128.72, 128.60, 126.80, 122.36, 119.45, 114.78,
55.56, 16.07. HRMS (ESI): m/z calcd for C17H17N2OS [M+H]+:
297.1056, found: 297.1059.
K. K. Eur. J. Med. Chem
(a)LaMattina, J. L.; McCarthy, P. A.; Reiter, L. A.; Holt,
W. F. J Med Chem. 1990 33, 543-552. (b) Mohareb, R.
M.; Zaki, M. Y.; Abbas, N. S. Steroids 2015 98, 80-91.
Nauen, R.; Ebbinghaus-Kintscher, U.; Salgado, V. L.;
Kaussmann, M.; Pest. Biochem. Physiol. 2003 76, 55-69.
(a) Hantzsch, A.; Weber, J. H. Ber. Dtsch. Chem. Ges.
1887 20, 3118. (b) Aguilar, E.; Meyers, A. I. Tetrahedron
Lett. 1994 35, 2473. (c) Ochiai, M.; Nishi, Y.; Hashimoto,
. 2013, 63, 924-934.
6
4.2.17 4-methyl-5-phenyl-N-(pyridin-2-yl)thiazol-2-amine (3q).
Yield: 83%, pale yellow solid, mp: 206.2-206.3°C; 1H NMR (500
MHz, DMSO-d6) δ 11.30 (s, 1H), 8.30 (dd, J = 4.9, 1.0 Hz, 1H),
7.69 (dd, J = 11.3, 4.2 Hz, 1H), 7.45 (dt, J = 15.1, 7.4 Hz, 4H),
7.30 (t, J = 7.1 Hz, 1H), 7.04 (d, J = 8.3 Hz, 1H), 6.91 (t, 1H),
2.36 (s, 3H). 13C NMR (125 MHz, DMSO-d6) δ 157.29, 152.08,
147.00, 142.24, 138.33, 133.36, 129.28, 128.71, 127.00, 122.29,
116.34, 111.26, 16.64. HRMS (ESI): m/z calcd for C15H14N3S
[M+H]+: 268.0903, found: 268.0909.
,
,
7
8
,
,
,
S.; Tsuchimoto, Y.; Chen, D. W. J. Org. Chem. 2003, 68,
7887.
9
(a) Kodomari, M.; Aoyama, T.; Suzuki, Y. Tetrahedron
Lett. 2002 43, 1717. (b) Aoyama, T; Murata, S; Arai, I.
Tetrahedron 2006 62, 3201-3213.
4.2.18 5-(4-chlorophenyl)-N,4-dimethylthiazol-2-amine (3r).
Yield: 96%, white solid, mp: 219.8-220.8°C; 1H NMR (500 MHz,
DMSO-d6) δ 7.58 (s, 1H), 7.39 (dd, J = 39.8,7.1 Hz, 4H), 2.82 (s,
,
,
,