F. V. Singh et al. / Tetrahedron 63 (2007) 10971–10978
10977
(327 mg, 92%) as a white solid; mp 138–149 ꢁC; Rf (CHCl3)
0.44; 1H NMR (200 MHz, CDCl3) d 2.28 (s, 3H, SCH3), 3.95
(s, 2H, CH2), 5.26 (br s, 2H, NH2), 6.72–6.81 (m, 2H, ArH),
6.90–6.99 (m, 2H, ArH), 7.11–7.19 (m, 3H, ArH), 7.29–7.37
chromatography (13% CHCl3/hexane) gave the title com-
pound 14b (293 mg, 89%) as a white solid; mp 192–
194 ꢁC; Rf (CHCl3) 0.43; 1H NMR (200 MHz, CDCl3)
d 1.02 (d, J¼6.2 Hz, 3H, CH3), 1.30–1.43 (m, 2H, CH2),
1.52–1.64 (m, 1H, CH), 1.70–1.79 (m, 2H, CH2), 1.86 (s,
3H, CH3), 3.26–3.34 (m, 4H, 2CH2), 5.04 (br s, 2H, NH2),
7.17–7.22 (m, 2H, ArH), 7.42–7.50 (m, 3H, ArH); IR
(KBr) 2219 (CN), 3341, 3411 (NH2) cmꢀ1; MS (FAB) 330
(M+).
(m, 3H, ArH); IR (KBr) 2214 (CN), 3343, 3424 (NH2) cmꢀ1
MS (FAB) 355 (M++1).
;
4.1.15. 3-Amino-6-methyl-5-methylsulfanyl-biphenyl-
2,4-dicarbonitrile 12a. A procedure similar to the one de-
scribed above for the preparation of 5a starting from 11a
(257 mg, 1 mmol), 4 (0.08 mL, 1.2 mmol) and chromato-
graphy (12% CHCl3/hexane) gave the title compound 12a
(262 mg, 94%) as a white solid; mp 220–222 ꢁC; Rf
4.1.20. 3-Amino-40-chloro-6-methyl-5-piperidin-1-yl-bi-
phenyl-2,4-dicarbonitrile 14c. A procedure similar to the
one described above for the preparation of 5a starting from
13c (324 mg, 1 mmol), 4 (0.08 mL, 1.2 mmol) and chroma-
tography (14% CHCl3/hexane) gave the title compound 14c
(315 mg, 90%) as a white solid; mp 210–212 ꢁC; Rf (CHCl3)
1
(CHCl3) 0.45; H NMR (200 MHz, CDCl3) d 2.16 (s, 3H,
CH3), 2.59 (s, 3H, SCH3), 5.12 (br s, 2H, NH2), 7.20–7.25
(m, 2H, ArH), 7.47–7.50 (m, 3H, ArH); IR (KBr) 2221
(CN), 3348, 3407 (NH2) cmꢀ1; MS (FAB) 280 (M++1);
HRMS calcd for C16H9N3S: 279.0830, found: 279.0846.
Anal. Calcd for C16H13N3S: C, 68.79; H, 4.69; N, 15.04.
Found: C, 68.88; H, 4.78; N, 15.16.
1
0.41; H NMR (200 MHz, CDCl3) d 1.62–1.68 (m, 6H,
3CH2), 1.87 (s, 3H, CH3), 3.26–3.32 (m, 4H, 2CH2), 5.04
(br s, 2H, NH2), 7.18 (d, J¼8.0 Hz, 2H, ArH), 7.46 (d,
J¼8.0 Hz, 2H, ArH); IR (KBr) 2213 (CN), 3351, 3414
(NH2) cmꢀ1; MS (FAB) 350 (M+); HRMS calcd for
C20H19ClN4: 350.1298, found: 350.1297.
4.1.16. 3-Amino-40-chloro-6-methyl-5-methylsulfanyl-bi-
phenyl-2,4-dicarbonitrile 12b. A procedure similar to the
one described above for the preparation of 5a starting from
11b (291 mg, 1 mmol), 4 (0.08 mL, 1.2 mmol) and chroma-
tography (10% CHCl3/hexane) gave the title compound 12b
(285 mg, 91%) as a white solid; mp 200–202 ꢁC; Rf (CHCl3)
0.48; 1H NMR (200 MHz, CDCl3) d 2.16 (s, 3H, CH3), 2.59
(s, 3H, SCH3), 5.15 (br s, 2H, NH2), 7.18 (d, J¼8.2 Hz, 2H,
ArH), 7.48 (d, J¼8.2 Hz, 2H, ArH); IR (KBr) 2221 (CN),
3350, 3413 (NH2) cmꢀ1; MS (FAB) 314 (M++1); HRMS
calcd for C16H12ClN3S: 313.0440, found: 313.0450.
Acknowledgements
This work was supported by the Department of Science and
Technology (DST), New Delhi. F.V.S. and V.K. thank Coun-
cil of Scientific and Industrial Research, New Delhi, for re-
search fellowships. Authors are thankful to SAIF, CDRI,
Lucknow for providing spectroscopic data.
4.1.17. 3-Amino-40-methoxy-6-methyl-5-methylsulfanyl-
biphenyl-2,4-dicarbonitrile 12c. A procedure similar to
the one described above for the preparation of 5a starting
from 11c (287 mg, 1 mmol), 4 (0.08 mL, 1.2 mmol) and
chromatography (13% CHCl3/hexane) gave the title com-
pound 12c (275 mg, 89%) as a white solid; mp 188–
190 ꢁC; Rf (CHCl3) 0.46; 1H NMR (200 MHz, CDCl3)
d 2.19 (s, 3H, CH3), 2.58 (s, 3H, SCH3), 3.87 (s, 3H,
OCH3), 5.13 (br s, 2H, NH2), 7.00 (d, J¼8.0 Hz, 2H,
ArH), 7.17 (d, J¼8.0 Hz, 2H, ArH); IR (KBr) 2228 (CN),
3364, 3432 (NH2) cmꢀ1; MS (FAB) 310 (M++1); HRMS
calcd for C17H15N3OS: 309.0936, found: 309.0935.
References and notes
1. (a) Sadek, K. U.; Selim, M. A.; Elmaghraby, M. A.; Elnagdi,
M. H. Pharmazie 1993, 48, 419; (b) Hartke, K.; Sauerbier,
M.; Richter, W. F. Arch. Pharm. (Weinheim, Ger.) 1992, 325,
279; (c) Gewald, K.; Schaefer, H. Z. Chem. 1981, 21, 183.
2. (a) Banzatti, C.; Mellini, P.; Salvadori, P. Gazz. Chim. Ital.
1987, 117, 259; (b) Dunn, J. P.; Ackerman, N. A.; Tomolonis,
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M. J.; Looney, A. M.; Burke, M. L. Eur. J. Med. Chem. 1992,
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S.; Kawashima, Y.; Hatayama, K. J. Med. Chem. 1999, 42,
1076; (b) Nakazato, A.; Sekiguchi, Y.; Ohta, K.; Chaki, S.;
Okuyama, S. Bioorg. Med. Chem. 1999, 7, 2027; (c) Boyle,
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A. Bioorg. Med. Chem. Lett. 2006, 16, 2734.
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Jimeno, M. L. Heterocycles 1993, 36, 2273; (b) Petersen, P. M.;
Wu, W.; Fenlon, E. E.; Kim, S.; Zimmer, S. C. Bioorg. Med.
Chem. 1996, 4, 1107.
5. Yu, Z.; Velasco, D. Tetrahedron Lett. 1999, 40, 3229.
6. (a) Modern Arene Chemistry; Astrue, D., Ed.; Wiley-VCH:
Weinheim, Germany, 2002; (b) Xi, C.; Chen, C.; Lin, J.;
Hong, X. Org. Lett. 2005, 7, 347; (c) Katritzsky, A. R.;
Belyakov, S. A.; Henderson, S. A.; Steel, P. J. J. Org. Chem.
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J. Org. Chem. 1997, 62, 5688.
4.1.18. 3-Amino-6-methyl-5-piperidin-1-yl-biphenyl-2,4-
dicarbonitrile 14a. A procedure similar to the one described
above for the preparation of 5a starting from 13a (294 mg,
1 mmol), 4 (0.08 mL, 1.2 mmol) and chromatography
(15% CHCl3/hexane) gave the title compound 14a
(291 mg, 92%) as a white solid; mp 210–212 ꢁC; Rf
1
(CHCl3) 0.40; H NMR (200 MHz, CDCl3) d 1.62–1.72
(m, 6H, 3CH2), 1.88 (s, 3H, CH3), 3.25–3.34 (m, 4H,
2CH2), 5.02 (br s, 2H, NH2), 7.20–7.24 (m, 2H, ArH),
7.44–7.50 (m, 3H, ArH); IR (KBr) 2218 (CN), 3346, 3409
(NH2) cmꢀ1; MS (FAB) 316 (M+); HRMS calcd for
C20H20N4: 316.1680, found: 316.1689.
4.1.19. 3-Amino-6-methyl-5-(4-methyl-piperidin-1-yl)-
biphenyl-2,4-dicarbonitrile 14b. A procedure similar to
the one described above for the preparation of 5a starting
from 13b (308 mg, 1 mmol), 4 (0.08 mL, 1.2 mmol) and