M. Filipan-Litvic´ et al. / Tetrahedron 64 (2008) 5649–5656
5655
1554, 1512, 1433, 1396, 1373, 1299, 1234, 1212, 1184, 1105, 1043,
1367, 1302, 1255, 1216, 1173, 1155, 1109, 1053, 1028 cmꢂ1
(CDCl3):
;
1H NMR
1018 cmꢂ1; 1H NMR (CDCl3):
d
¼2.36 (s, 3H, CH3), 2.58 (s, 6H, CH3),
d
¼0.89 (t, 6H, CH2CH3, J¼7.1), 0.98 (t, 6H, CH2CH2CH3),
3.56 (s, 6H, OMe), 7.13 (d, 2H, J¼8.0 Hz), 7.18 (d, 2H, J¼8,0 Hz); 13C
1.74–1.82 (m, 4H, CH2CH2CH3), 2.78–2.83 (m, 4H, CH2CH2CH3), 3.98
(q, 4H, CH2CH3, J¼14.3), 7.24–7.28 (m, 2H), 7.34–7.36 (m, 3H); 13C
NMR (CDCl3):
d
¼21.0, 22.6, 51.9, 127.0, 127.4, 128.7, 133.1, 138.1,
146.0 155.1,168.3; Anal. Calcd for C18H19NO4: C 68.99, H 6.11, N 4.47;
found: C 68.8, H 6.0, N 4.4.
NMR (CDCl3):
d
¼13.5, 14.0, 23.1, 38.3, 61.2, 126.7, 128.0, 128.2, 128.3,
136.7, 146.0, 159.1, 168.0; Anal. Calcd for C23H29NO4: C 72.04, H 7.62,
N 3.65; found: C 71.8, H 7.5, N 3.6.
4.3.4. 2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(2,4-dimethyl-
phenyl)-pyridine (46)
Acknowledgements
Pale yellow oil; yield: 0.29 g (89%); Rf (CH2Cl2/EtOAc, 9:1)¼0.32;
IR (film):
n
¼2953, 2924, 1736, 1614, 1561, 1501, 1435, 1403, 1379,
1331, 1294, 1239, 1211, 1193, 1150, 1120, 1103, 1039 cmꢂ1
(CDCl3):
¼2.05 (s, 3H, Me), 2.32 (s, 3H, Me), 2.59 (s, 6H, Me), 3.51
(s, 6H, OMe), 6.89–6.97 (m, 2H), 7.00 (s, 1H); 13C NMR (CDCl3):
;
1H NMR
The authors wish to express their gratitude to the Belupo
Pharmaceuticals Inc. for financial support of this research.
d
d
¼19.5, 21.1, 22.9, 51.9, 125.6, 127.0, 128.1, 130.2, 132.1, 135.6, 138.0,
References and notes
146.5, 155.2, 168.0; Anal. Calcd for C19H21NO4: C 69.71, H 6.47, N
4.28; found: C 69.6, H 6.4, N 4.0.
1. Berkels, B.; Roesen, R.; Dhein, S.; Fricke, U.; Klaus, W. Cardiovasc. Drug Rev. 1999,
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4.3.5. 2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(5-bromothienyl)-
pyridine (52)
Pale yellow crystals; yield: 0.34 g (88%); Rf (CH2Cl2/EtOAc,
9:1)¼0.42; mp 110.0–112.0 ꢀC; IR (KBr):
¼2953, 1732, 1559, 1530,
n
1433, 1400, 1374, 1337, 1238, 1208, 1125, 1102, 1037 cmꢂ1; 1H NMR
(CDCl3):
d
¼2.57 (s, 6H, Me), 3.73 (s, 6H, OCH3), 6.81–6.82 (d, 2H,
J¼3.8 Hz), 7.01 (d, 2H, J¼3.8 Hz); 13C NMR (CDCl3):
¼22.8, 52.5,
d
114.6, 126.9, 128.8, 130.0, 137.2, 137.5, 155.6, 167.9; Anal. Calcd for
C
15H14BrNO4S: C 46.89, H 3.67, Br 20.80, N 3.65, S 8.34; found: C
8. Peri, R.; Padmanabhan, S.; Singh, S.; Rutledge, A.; Triggle, D. J. J. Med. Chem.
2000, 43, 2906–2914.
46.7, H 3.5, Br 20.0, N 3.6, S 8.3.
9. Zhou, X.; Zhang, L.; Tseng, E.; Scott-Ramsay, E.; Schentag, J. J.; Coburn, R. A.;
Morris, M. E. Drug Metab. Dispos. 2005, 33, 321–328.
10. Bo¨cker, R. H.; Guengerich, F. P. J. Med. Chem. 1986, 28, 1596–1603.
11. Kudo, S.; Okumura, H.; Miyamoto, G.; Ishizaki, T. Drug Metab. Dispos. 1999, 27,
303–308.
12. The Merck Index, 13th ed.; Merck Research Laboratories: New Jersey, NJ, 2001;
6370.
13. (a) Mohr, E.; Schneider, W. J. Prakt. Chem. 1904, 69, 245–264; (b) Kro¨hnke, F.;
Ahrenhok, G. M.; Gross, K. F. J. Prakt. Chem. 1960, 11, 256–264.
4.3.6. 2,6-Dimethyl-3,5-dimethoxycarbonyl-4-(40-biphenyl)-
pyridine (54)
Pale yellow needles; yield: 0.35 g (93%); Rf (CH2Cl2/EtOAc,
9:1)¼0.23; mp 143.0–145.0 ꢀC; IR (KBr):
¼1727, 1599, 1567, 1519,
n
1488, 1436, 1401, 1373, 1335, 1298, 1243, 1192, 1157, 1110, 1044,
1008 cmꢂ1; 1H NMR (CDCl3):
d
¼2.63 (s, 6H, Me), 3.58 (s, 6H, OMe),
7.32–7.50 (m, 6H), 7.57–7.73 (m, 4H); 13C NMR (CDCl3):
d
¼22.9, 52.1,
14. (a) Go¨rlitzer, K.; Buß, D. Arch. Pharm. (Weinheim, Ger.) 1981, 314, 949–954; (b)
Zolfigol, M. A.; Kiany-Borazjani, M.; Sadeghi, M. M.; Memarian, H. R.; Mo-
hammadpoor-Baltork, I. Synth. Commun. 2000, 30, 2945–2950; (c) Zolfigol, M.
A.; Kiany-Borazjani, M.; Sadeghi, M. M.; Mohammadpoor-Baltork, I.; Memarian,
H. R. Synth. Commun. 2000, 30, 3919–3923; (d) Zolfigol, M. A.; Kiany-Borazjani,
M.; Sadeghi, M. M.; Mohammadpoor-Baltork, I.; Memarian, H. R. Synth. Com-
mun. 2000, 30, 551–558; (e) Niknam, K.; Zolfigol, M. A.; Razavian, S. M.; Mo-
hammadpoor-Baltork, I. Heterocycles 2005, 65, 657–660; (f) Zolfigol, M. A.;
Shirini, F.; Choghamarani, A. G.; Mohammadpoor-Baltork, I. Phosphorus Sulfur
Silicon 2003, 178, 1709–1715; (g) Zolfigol, M. A.; Choghamarani, A. G.; Dialameh,
S.; Sadeghi, M. M.; Mohammadpoor-Baltork, I.; Memarian, H. R. J. Chem. Res.
2003, 18–20; (h) Hashemi, M. M.; Ghafuri, H.; Karimi-Jaberi, Z. Monatsch. Chem.
2006, 134, 197–200; (i) Zolfigol, M. A.; Bagherzadeh, M.; Niknam, K.; Shirini, F.;
Mohammadpoor-Baltork, I.; Choghamarani, A. G.; Baghbanzadeh, M. J. Iran.
Chem. Soc. 2006, 3, 73–80; (j) Niknam, K.; Zolfigol, M. A.; Razavian, S. M.;
Mohammadpoor-Baltork, I. J. Heterocycl. Chem. 2006, 43, 199–202.
15. (a) Itoh, T.; Nagata, K.; Matsuya, Y.; Miyazaki, M.; Ohsawa, A. J. Org. Chem. 1997,
62, 3582–3585; (b) Zhu, X. Q.; Zhao, B. J.; Cheng, J. P. J. Org. Chem. 2000, 65,
8158–8163; (c) Zolfigol, M. A.; Zebarjadian, M. H.; Sadegh, M. M.; Mo-
hammadpoor-Baltork, I.; Memarian, H. R.; Shamsipur, M. Synth. Commun. 2001,
31, 929–934.
16. (a) Mashraqui, S. H.; Karnik, M. A. Synthesis 1998, 713–714; (b) Khadilkar, B.;
Borkar, S. Synth. Commun. 1998, 28, 207–212; (c) Pfister, J. R. Synthesis 1990,
689–690; (d) Sabitha, G.; Kiran Kumar Reddy, G. S.; Reddy, Ch. S.; Fatima, N.;
Yadav, J. S. Synthesis 2003, 1267–1271; (e) Balogh, M.; Hermecz, I.; Me´sza´ros, Z.;
Laszlo, P. Helv. Chim. Acta 1984, 67, 2270–2272.
17. (a) Meyer, H.; Wehinger, E.; Bossert, F.; Scherling, D. Arzneim.-Forsch. (Drug. Res.)
1983, 33, 106–112; (b) Sadeghi, M. M.; Mohammadpoor-Baltork, I.; Memarian,
H. R.; Sobhani, S. Synth. Commun. 2000, 30, 1661–1665; (c) Vanden Eynde, J. J.;
Mayence, A.; Maquestiau, A. Tetrahedron 1992, 48, 463–468; (d) Wang, B.; Hu,
Y.; Hu, H. Synth. Commun. 1999, 29, 4193–4199; (e) Zolfigol, M. A.; Sadeghi, M.
M.; Mohammadpoor-Baltork, I.; Choghamarani, A. G.; Taqian-Nasab, A. Asian J.
Chem. 2001, 13, 887–890; (f) Zolfigol, M. A.; Salehi, P.; Ghorbani-Choghamarani,
A.; Safaiee, M.; Shahamirian, M. Synth. Commun. 2007, 37, 1817–1823.
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126.6, 126.7, 126.9, 127.6, 128.1, 128.8, 135.2, 140.0, 141.0, 145.7,
155.5, 168.4; Anal. Calcd for C23H21NO4: C 73.58, H 5.64, N 3.73;
found: C 73.5, H 5.5, N 3.7.
4.3.7. 2,6-Dimethyl-3,5-diisopropoxycarbonyl-4-phenyl-pyridine
(56)
Pale yellow crystals; yield: 0.33 g (93%); Rf (CH2Cl2/EtOAc,
9:1)¼0.37; mp 84.0–89.0 ꢀC; IR (KBr):
n
¼2979, 1727, 1714, 1555,
1536, 1455, 1374, 1290, 1234, 1095, 1036 cmꢂ1
;
1H NMR (CDCl3):
d
¼0.86 (d, 12H, CHMe2, J¼6.2), 2.51 (s, 6H, Me), 4.80–4.84 (m, 2H,
CHMe2), 7.18–7.19 (m, 2H); 7.27–7.28 (m, 3H); 13C NMR (CDCl3):
d
¼20.7, 22.3, 68.5, 126.7, 127.4, 127.5, 127.8, 127.9, 135.9, 145.1, 154.5,
166.8; Anal. Calcd for C21H25NO4: C 70.96, H 7.09, N 3.94; found: C
70.8, H 6.9, N 3.8.
4.3.8. 2,6-Dimethyl-3,5-di-(tert-butoxycarbonyl)-4-phenyl-
pyridine (57)
Colourless crystals; yield: 0.32 g (83%); Rf (CH2Cl2/EtOAc,
9:1)¼0.41; mp 88.0–92.0 ꢀC; IR (KBr):
¼3437, 3064, 3004, 2996,
n
2983, 2931, 1731, 1719, 1563, 1496, 1476, 1457, 1410, 1393, 1366,
1305, 1251, 1157, 1107, 1076, 1045, 1026 cmꢂ1 1H NMR (CDCl3):
;
d
¼1.18 (s, 18H, CMe3), 2.58 (s, 6H, Me), 7.26–7.29 (m, 2H), 7.36–7.37
(m, 3H); 13C NMR (CDCl3):
d
¼22.7, 27.5, 82.2, 127.8, 128.0, 128.2,
128.8, 136.4, 145.0, 154.3, 166.9; Anal. Calcd for C23H29NO4: C 72.04,
H 7.62, N 3.65; found: C 71.8, H 7.5, N 3.6.
19. (a) Vanden Eynde, J. J.; D’Ozario, R.; Van Haverbeke, Y. Tetrahedron 1994, 50,
2479–2484; (b) Choudary, B. M.; Valli, V. L. K.; Durga Prasad, A. Synth. Commun.
1991, 21, 2007–2013; (c) Kamal, A.; Ahmad, M.; Mohd, N.; Hamid, A. M. Bull.
Chem. Soc. Jpn. 1964, 37, 610–612; (d) Vanden Eynde, J. J.; Delfosse, F.; Mayence,
A.; Van Haverbeke, Y. Tetrahedron 1995, 51, 6511–6516; (e) Bagley, M. C.; Lubinu,
4.3.9. 2,6-Di-n-propyl-3,5-dimethoxycarbonyl-4-phenyl-
pyridine (58)
Pale yellow oil; yield: 0.38 g (99%); Rf (CH2Cl2/EtOAc, 9:1)¼0.35;
IR (film):
n
¼2964, 2934, 2873, 1728, 1557, 1496, 1465, 1446, 1385,