7
140.5 (C), 140.9 (C), 143.6 (C), 143.7 (C), 150.4 (CH), 150.7 (2 CH), 152.6
(C). LC/MS (ESI+) tr = 3.32 min m/z 273.41, 275.38 [M+H] +. IR (KBr) Ʋ:
3047, 2920, 1587, 1384, 808 cm-1. HRMS (ESI+) m/z 273.0253 [M+H]+,
calcd for C14H9ClN2S+H 273.0255.
3-Methyl-2-(5-(pyridin-2-yl)thiophen-2-yl)pyridine 16. MW: 252.33 g/mol.
ACCEPTED MANUSCRIPT
yellow solid (115 mg, 32 %). Mp: 96 °C. Eluent: gra dient of solvent from
cyclohexane to cyclohexane/EtOAc (8/2). Washing with EtOEt. 1H NMR
(CDCl3, 400 MHz): δ 2.6 (s, 3H), 7.13 (dd, 1H, J = 4.8 Hz and J = 7.6 Hz),
7.54-7.56 (m, 2H), 7.66 (d, 1H, J = 4.0 Hz), 7.70 (m, 2H), 8.49 (dd, 1H, J =
1.1 Hz and J = 4.8 Hz), 8.60 (dt, 2H, J = 1.3 Hz and J = 4.9 Hz). 13C NMR
(CDCl3, 100 MHz): δ 21.6 (CH3), 119.1 (CH), 121.9 (CH), 122.1 (CH),
125.3 (CH), 128.1 (CH), 129.9 (C), 136.7 (CH), 139.4 (CH), 145.6 (C),
146.5 (C), 147.0 (CH), 149.7 (CH), 151.2 (C), 152.5 (C). LC/MS (ESI+) tr =
4.52 min m/z 253.43 [M+H] +. IR (KBr) Ʋ: 2967, 1582, 1413, 1296, 780 cm-
1. HRMS (ESI+) m/z 253.0720 [M+H]+, calcd for C15H12N2S+H 253.0721.
2-Chloro-3-(5-(pyridin-4-yl)thiophen-2-yl)pyridine 12. MW: 272.75 g/mol.
White solid (250 mg, 48 %). Mp: 152 °C. Eluent: gra dient of solvent from
1
cyclohexane to EtOAc. H NMR (CDCl3, 400 MHz): δ 7.33 (dd, J = 4.8 Hz
and J = 8 Hz, 1H), 7.48 (d, J = 4.0 Hz, 1H), 7.51-7.52 (m, 2H), 7.53 (d, J =
4 Hz, 1H), 7.90 (dd, J = 1.6 Hz and J = 7.6 Hz, 1H), 8.39 (dd, J = 2.0 Hz
and J = 4.8 Hz, 1H), 8.62-8.64 (m, 2H). 13C NMR (CDCl3, 100 MHz): δ
119.8 (2CH), 122.6 (CH), 125.6 (CH), 129.5 (C), 129.7 (CH), 139.2 (CH),
139.6 (C), 140.8 (C), 142.7 (C), 148.6 (CH), 148.9 (C), 150.5 (2CH).
LC/MS (ESI+) tr = 3.09 min m/z 273.54/275.52 [M+H] +. IR (KBr) Ʋ: 3070,
3051, 1586, 1403, 801 cm-1. HRMS (ESI+) m/z 273.0258 [M+H]+, calcd for
C14H9ClN2S+H 273.0253.
3-Methyl-2-(5-(pyridin-4-yl)thiophen-2-yl)pyridine 17. MW: 252.33 g/mol.
yellow solid (130 mg, 30 %). Mp: 112 °C. Eluent: gr adient of solvent from
cyclohexane to cyclohexane/EtOAc (1/1). 1H NMR (CDCl3, 400 MHz): δ
7.15 (dd, 1H, J = 4.8 Hz and J = 7.6 Hz), 7.48-7.55 (m, 2H), 7.55 (dd, 1H, J
= 0.8 Hz and J = 7.6 Hz), 8.49 (dd, 1H, J = 1.2 Hz and J = 4.8 Hz), 8.60-
8.61 (m, 2H). 13C NMR (CDCl3, 100 MHz): δ 21.5 (CH3), 119.6 (2 CH),
122.1 (CH), 125.8 (CH), 127.8 (CH), 129.8 (C), 139.5 (CH), 141.2 (C),
142.0 (C), 146.9 (CH), 147.1 (C), 150.3 (2 CH), 150.5 (C). LC/MS (ESI+) tr
= 3.15 min m/z 253.43 [M+H] +. IR (KBr) Ʋ: 2927, 1595, 1415, 1122, 800
cm-1HRMS (ESI+) m/z 253.0799 [M+H]+, calcd for C15H12N2S+H 253.0800.
2-Methoxy-5-(5-(pyridin-4-yl)thiophen-2-yl)pyridine 13. MW: 268.33 g/mol.
yellow solid (270 mg, 60 %). Mp: 111 °C. Eluent: gr adient of solvent from
cyclohexane to cyclohexane/EtOAc (4/6). 1H NMR (CDCl3, 400 MHz): δ
3.98 (s, 3H), 6.81 (dd, J = 8.6 Hz and J = 0.8 Hz, 1H), 7.24 (d, J = 3.8 Hz,
1H), 7.50-7.44 (m, 3H), 7.80 (dd, J = 8.6 Hz and J = 2.6 Hz, 1H), 8.46 (dd,
J = 2.6 Hz and J = 0.8 Hz, 1H), 8.62-8.56 (m, 2H). 13C NMR (CDCl3, 100
MHz): δ 53.9 (CH3), 111.3 (CH), 119.6 (2 CH), 123.6 (C), 124.2 (CH),
126.5 (CH), 136.4 (CH), 140.1 (C), 141.2 (C), 142.7 (C), 144.2 (CH), 150.6
(2 CH), 164.1 (C). LC/MS (ESI+) tr = 3.31 min m/z 269.56 [M+H] +. IR (KBr)
Ʋ 2924, 2850, 1594, 1011, 805 cm-1. HRMS (ESI+) m/z 269.0747 [M+H]+,
calcd for C15H12N2OS+H 269.0749.
2-(4-Methoxyphenyl)-5-phenylthiophene 18.47 C17H14OS. MW: 266.36
g/mol. White solid (250 mg, 50%). Mp: 165°C (lit.: 163-165 °C). 55 Eluent:
gradient of solvent from Cyclohexane to Cyclohexane/CH2Cl2 9/1. 1H NMR
(CDCl3, 400 MHz): δ 3.80 (s, 3H), 6.99 (d, J = 4.8 Hz, 2H), 7.28-7.32 (m,
1H), 7.40-7.44 (m, 3H), 7.50 (d, J = 3.6 Hz, 1H), 7.62 (d, J = 8.8 Hz, 2H),
7.67 (d, J = 7.2 Hz, 2H). 13C NMR (CDCl3, 100 MHz): δ 55.2 (CH3), 114.5
(2 CH), 123.6 (CH), 124.8 (CH), 125.0 (2 CH), 126.1 (C), 126.5 (2 CH),
127.5 (CH), 129.1 (2 CH), 133.5 (C), 141.3 (C), 142.6 (C), 158.9 (C).
LC/MS (ESI+) tr = 6.05 min m/z [M+H] + not ionize.
2-Nitro-5-(5-(pyridin-2-yl)thiophen-2-yl)pyridine 14. MW: 283.30 g/mol.
Orange solid (216 mg, 40 %). Mp: 232 °C. Eluent: gr adient of solvent from
cyclohexane to EtOAc. 1H NMR (CDCl3, 400 MHz): δ 7.23-7.26 (m, 1H),
7.57 (d, J = 4.0 Hz, 1H), 7.63 (d, J = 4.0 Hz, 1H), 7.71-7.76 (m, 2H), 8.20
(dd, J = 2.4 Hz and J = 8.8 Hz, 1H), 8.31 (dd, J = 0.4 Hz and J = 8.4 Hz,
1H), 8.61-8.63 (m, 1H), 8.92 (d, J = 200 Hz, 1H). 13C NMR (CDCl3, 100
MHz): δ 118.6 (CH), 118.9 (CH), 123.0 (CH), 125.7 (CH), 127.7 (CH),
135.3 (CH), 135.9 (C), 136.9 (CH), 138.9 (C), 145.2 (CH), 148.4 (C), 149.8
(CH), 151.4 (C), 155.2 (C). LC/MS (ESI+) tr = 4.53 min m/z 284.56 [M+H] +.
IR (KBr) Ʋ: 3061, 2924, 1530, 1335, 777 cm-1. HRMS (ESI+) m/z 284.0496
[M+H]+, calcd for C14H9N3O2S+H 284.0494.
5-(5-(Pyrimidin-5-yl)thiophen-2-yl)furan-2-carbaldehyde 19. MW: 256.28
g/mol. yellow solid (120 mg, 40 %). Decomposition at 250°C. Eluent:
gradient of solvent from CH2Cl2 to CH2Cl2/MeOH (9/1). 1H NMR (CDCl3,
400 MHz): δ 6.77 (d, 1H, J = 4.0 Hz), 7.33 (d, 1H, J = 4.0 Hz), 7.44 (d, 1H,
J = 4.0 Hz), 7.57 (d, 1H, J = 4.0 Hz), 8.99 (s, 2H), 9.17 (s, 1H), 9.66 (s,
1H). 13C NMR (CDCl3, 100 MHz): δ 108.4 (CH), 123.3 (CH), 126.2 (CH),
127.2 (CH), 127.9 (C), 133.1 (C), 137.8 (C), 151.8 (C), 153.4 (2CH), 153.6
(C), 157.8 (CH), 176.9 (CHO). LC/MS (ESI+) tr = 4.06 min m/z 257.42
[M+H] . IR (KBr) Ʋ: 3124, 2917, 1669, 1450, 778 cm-1. HRMS (ESI+) m/z
+
4-Methyl-3-(5-(pyridin-2-yl)thiophen-2-yl)pyridine 15. MW: 252.33 g/mol.
257.0304 [M+H]+, calcd for C13H8N2O2S+H 257.0306.
yellow oil (175 mg, 40 %). Eluent: gradient of solvent from cyclohexane to
1
cyclohexane/EtOAc (1/1). H NMR (CDCl3, 400 MHz): δ 2.51 (s, 3H), 7.14
(d, J = 3.8 Hz, 1H), 7.15-7.22 (m, 2H), 7.59 (d, J = 3.8 Hz, 1H), 7.66-7.75
(m, 2H), 8.44 (d, J = 5.0 Hz, 1H), 8.57-8.60 (m, 1H), 8.67 (s, 1H). 13C NMR
(CDCl3, 100 MHz): δ 20.8 (CH3), 118.8 (CH), 122.3 (CH), 124.8 (CH),
125.7 (CH), 128.5 (CH), 130.7 (C), 136.9 (CH), 141.0 (C), 145.1 (C), 145.8
(C), 148.9 (CH), 149.8 (CH), 150.1 (CH), 152.4 (C). LC/MS (ESI+) tr = 3.16
5. Acknowledgments
The authors warmly thank Prof Pierre Verhaeghe for his
contribution to the proofreading of this paper, and the Centre de
Ressources Informatiques de Haute Normandie (CRIHAN) for
the molecular modelling software.
+
min m/z 253.56 [M+H] . IR (KBr) Ʋ: 3047, 2934, 1584, 1431, 774 cm-1.
HRMS (ESI+) m/z 253.0802 [M+H]+, calcd for C15H12N2S+H 253.0799.
6. References
10 R. Rossi, F. Bellina, M. Lessi, C. Manzini, Adv. Synth. Catal. 2014, 356,
17-117.
11 S. Yanagisawa, T. Sudo, R. Noyori, K. Itami, J. Am. Chem. Soc. 2006,
128, 11748-11749.
1 A. Deep, B. Narasimhan, S. Aggarwal, D. Kaushik, A. K. Sharma, Cent.
Nerv. Syst. Agents Med. Chem. 2016, 16, 158-164.
12 D. Alberico, M. E. Scott, M. Lautens, Chem. Rev. 2007, 107, 174-238.
13 T. Satoh, M. Miura, Chem. Lett. 2007, 36, 200-205.
14 Y. Li, J. Wang, M. Huang, Z. Wang, Y. Wu, Y. Wu, J. Org. Chem. 2014,
79, 2890−2897.
15 M. H. Daniels, J. R. Armand, K. L. Tan, Org. Lett., 2016, 18, 3310-3313.
16 T. Murai, T. Yamauchi, F. Shibahara, Org. Lett. 2015, 17, 5392-5395.
17 J. Fournier dit Chabert, B. Marquez, L. Neville, L. Joucla, S. Broussous, P.
Bouhours, E. David, S. Pellet-Rostaing, B. Marquet, N. Moreau, M. Lemaire,
Bioorg. Med. Chem. 2007, 15, 4482–4497.
18 T. Okazawa, T. Satoh, M. Miura, M. Nomura, J. Am. Chem. Soc. 2002,
124, 5286-5287.
19 S. Bensaid, J. Roger, K. Beydoun, D. Roy, H. Doucet, Synth. Commun.
2011, 41, 3524-3531.
2 J. B. Sperry, D. L. Wright, Curr. Opin. Drug Discov. Devel. 2005, 8, 723-
740.
3 R. P. Sheridan, J. Chem. Inf. Comput. Sci. 2002, 42, 103-108.
4 J. Yuan, S. Venkatraman, Y. Zheng, B. M. McKeever, L. W. Dillard, S. B.
Singh, J. Med. Chem. 2013, 56, 4156-4180.
5 D. T. Moir, Y. Xiang, A. C. Arvanites, S. M. Ali, B. Geng, M. A. Ashwell,
H. A. Orgueira, PCT Int. Appl. 2004, WO 2004064837 A1 20040805.
6 K. Y. Jun, H. Kwon, S. E. Park, E. Lee, R. Karki, P. Thapa, J. H. Lee, E. S.
Lee, Y. Kwon, Eur. J. Med Chem. 2014, 80, 428-438.
7 K. Masui, A. Mori, K. Okano, K. Takamura, M. Kinoshita, T. Ikeda, Org.
Lett. 2004, 6, 2011-2014.
8 N. Koumura, Z. S. Wang, S. Mori, M. Miyashita, E. Suzuki, K. Hara, J.
Am. Chem. Soc. 2006, 128, 14256-14257.
9 J. Wencel-Delord, F. Glorius, Nat. Chem. 2013, 5, 369-375.
20 T. Satoh, M. Miura, Chem. Lett. 2007, 36, 200-205.