B. E. Blass et al. / Tetrahedron Letters 47 (2006) 3177–3180
3179
8173; (c) Bunin, B. A. The Combinatorial Index; Academic
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Society, 1997.
20. Representative procedure: 4-amino-2-(methylthio) pyrim-
idine-5-carbaldehyde (100 mg, 0.55 mmol) and ethyl 2-
phenylacetate (89 mg, 86.9 lL, 0.55 mmol) are dissolved in
5.0 mL DMA, 634 mg of KF/Al2O3 (40 wt %, KF, Sigma–
Aldrich catalog #316385) is added, and the reaction is
stirred for 15 min. The reaction is then filtered, the
residual solid is washed with 15 mL CH2Cl2, and the
combined organic solvents are stripped to a solid. Puri-
fication by flash chromatography with 3/1 hexane/EtOAc
on silica gel provided 131 mg (85%) of the desired product,
8-methyl-2-(methylthio)-6-phenylpyrido[2,3-d]pyrimidin-7
(8H)-one. Data from Table 1. Entry 1: 1H NMR
(300 MHz, CDCl3): d 8.61 (s, 1H), 7.65 (s, 1H), 7.6 (d,
2H, J = 6.3 Hz), 7.37 (m, 3H), 3.76 (s, 3H), 2.59 (s, 3H);
(M+H+) 284. Entry 2: 1H NMR (300 MHz, CDCl3): d
8.65 (s, 1H), 7.58 (s, 1H), 7.27 (m, 4H), 3.82 (s, 3H), 2.68
(s, 3H), 2.23 (s, 3H); (M+H+) 298. Entry 3: 1H NMR
(300 MHz, CD3OD): d 8.20 (s, 1H), 7.95 (s, 1H), 7.58 (d,
2H, J = 7.6 Hz), 6.88 (d, 2H, J = 7.8 Hz), 3.83 (s, 3H),
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10. Ellingboe, J. W.; Collini, M. D.; Quagliato, D.; Chen, J.;
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1
2.70 (s, 3H); (M+H+) 300. Entry 4: H NMR (300 MHz,
CDCl3): d 8.65 (s, 1H), 7.69 (s, 1H), 7.68 (d, 2H,
J = 8.7 Hz), 6.97 (d, 2H, J = 8.6 Hz), 3.86 (s, 3H), 3.80
(s, 3H), 2.62 (s, 3H); (M+H+) 314. Entry 5: 1H NMR
(300 MHz, CDCl3): d 8.64 (s, 1H), 7.69 (s, 1H), 6.94 (m,
3H), 3.83 (s, 3H), 3.81 (s, 3H), 3.78 (s, 3H), 2.69 (s, 3H);
(M+H+) 344. Entry 6: 1H NMR (300 MHz, CDCl3): d
8.62 (s, 1H), 7.67 (s, 1H), 7.61 (d, 2H, J = 8.4 Hz), 7.43 (d,
2H, J = 8.3 Hz), 3.80 (s, 3H), 2.63 (s, 3H), 1.33 (s, 9H);
(M+H+) 340. Entry 7: 1H NMR (300 MHz, CDCl3): d
8.68 (s, 1H), 7.63 (s, 1H), 7.44 (d, 2H, J = 7.1 Hz), 7.31 (d,
1H, J = 6.8 Hz), 3.81 (s, 3H), 2.69 (s, 3H); (M+H+) 352.
12. Beylin, V. G.; Blackburn, A. C.; Erdman, D.T.; Toogood,
P. L. WO 05005426, 2005.
13. Cheresh, D. A.; Paul, R.; Eliceiri, B. U.S. 2004214836,
2004; Vu, C. B.; Luke, G. P.; Kawahata, N.; Shakespeare,
W. C.; Wang, Y.; Sundaramoorthi, R.; Metcalf, C. A.;
Keenan, T. P.; Pradeepan, S.; Corpuz, E.; Merry, T.;
Bohacek, R. S.; Dalgarno, D. C.; Narula, S. S.; Van
Schravendijk, M. R.; Ram, M. K.; Adams, S.; Liou, S.;
Keats, J. A.; Violette, S. M.; Guan, W.; Weigele, M.;
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14. Goldstein, D. M.; Lim, J. A. WO 04014907, 2004; Chen, J.
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02064594, 2002; Arzeno, H. B.; Chen, J. J.; Dunn, J. P.;
Goldstein, D. M.; Lin, J. A. WO 02018379, 2002
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E.; Kempf, D. J.; McDaniel, K. F.; Maring, C. J.; Stoll, V.
S.; Zhang, R. U.S. 2004167123, 2004.
1
Entry 8: H NMR (CDCl3): d 8.63 (s, 1H), 7.56 (s, 1H),
7.27 (m, 4H), 4.56 (q, 2H, J = 7.0 Hz), 2.67 (s, 3H), 2.24 (s,
1
3H), 1.38 (t, 3H, J = 7.0 Hz); (M+H+) 312. Entry 9: H
NMR (300 MHz, CDCl3): d 8.58 (s, 1H), 7.70 (s, 1H), 7.50
(d, 2H, J = 8.7 Hz), 6.85 (d, 2H, J = 9.5 Hz), 4.51 (q, 2H,
J = 7.1 Hz), 2.58 (s, 3H), 1.53 (br s, 1H), 1.28 (t, 3H,
J = 7.1 Hz); (M+H+) 314. Entry 10: 1H NMR (CDCl3): d
8.96 (s, 1H), 7.67 (s, 1H), 7.65 (d, 2H, J = 8.8 Hz), 6.99 (d,
2H, J = 8.8 Hz), 4.57 (q, 2H, J = 7.0 Hz), 3.87 (s, 3H),
2.67 (s, 3H), 1.39 (t, 3H, J = 7.0 Hz); (M+H) 328. Entry
11: 1H NMR (CDCl3): d 8.49 (s, 1H), 7.60 (s, 1H), 6.95 (m,
3H), 4.42 (q, 2H, J = 7.0 Hz), 3.68 (s, 3H), 3.65 (s, 3H),
2.53 (s, 3H), 1.25 (t, 3H, J = 7.1 Hz); (M+H+) 358. Entry
12: 1H NMR (CDCl3): d 8.55 (s, 1H), 7.66 (s, 1H), 7.52 (d,
2H, J = 8.6 Hz), 7.39 (d, 2H, J = 8.6 Hz), 4.49 (q, 2H,
J = 7.0 Hz), 2.49 (s, 3H), 1.28 (t, 3H, J = 7.0 Hz), 1.26 (s,
9H); (M+H+) 354. Entry 13: 1H NMR (300 MHz,
CDCl3): d 8.71 (s, 1H), 7.63 (s, 1H), 7.45 (d, 2H, J =
7.5 Hz), 7.32 (d, 1H, J = 7.1 Hz), 4.59 (q, 2H, J = 6.5 Hz),
2.69 (s, 3H), 1.42 (t, 3H, J = 5.6 Hz); (M+H+) 366. Entry
16. Yamada, K.; Hikota, M.; Koga, Y.; Yoshikawa, K.;
Omori, K. JP 2004083587, 2004.
17. Angiolini, M.; Ballinari, D.; Bassini, D. F.; Bonomini, L.;
Gude, M.; Menichincheri, M.; Moll, J.; Trosset, J. Y. U.S.
2004009993, 2004.
18. Barsanti, P. A.; Bussiere, D.; Harrison, S. D.; Heise, C. C.;
Jansen, J. M.; Jazan, E.; Machajewski, T. D.; Mcbride, C.;
McCrea, W. R.; Ng, S.; Ni, Z. J.; Pecchi, S.; Pfister, K.;
Ramurthy, S.; Renhowe, P. A.; Shafer, C. M.; Silver, J. B.;
Wagman, A.; Weismann, M. WO 04018419, 2004.
19. (a) Klutchko, S. R.; Hamby, J. M.; Boschelli, D. H.; Wu,
Z.; Kraker, A. J.; Amar, A. M.; Hartl, B. G.; Shen, C.;
Klohs, W. D.; Steinkampf, R. W.; Driscoll, D. L.; Nelson,
J. M.; Elliott, W. L.; Roberts, B. J.; Stoner, C. L.; Vincent,
P. W.; Dykes, D. J.; Panek, R. L.; Lu, G. H.; Major, T. C.;
Dahring, T. K.; Hallak, H.; Bradford, L. A.; Showalter,
H. D. H.; Doherty, A. M. J. Med. Chem. 1998, 41, 3276–
3292; (b) Boschelli, D. H.; Wu, Z.; Klutchko, S. R.;
Showalter, H. D. H.; Hamby, J. M.; Lu, G. H.; Major, T.
C.; Dahring, T. K.; Batley, B.; Panek, R. L.; Keiser, J.;
Hartl, B. G.; Kraker, A. J.; Klohs, W. D.; Roberts, B. J.;
Patmore, S.; Elliott, W. L.; Steinkampf, R.; Bradford, L.
A.; Hallak, H.; Doherty, A. M. J. Med. Chem. 1998, 41,
4365–4377.
1
14: H NMR (300 MHz, CDCl3): d 8.62 (s, 1H), 7.53 (s,
1H), 7.27 (m, 4H), 3.08 (m, 1H), 2.71 (s, 3H), 2.23 (s, 3H),
1.35 (q, 2H, J = 11 Hz), 0.99 (m, 2H); (M+H+) 324. Entry
1
15: H NMR (300 MHz, CD3OD): d 8.76 (s, 1H), 7.87 (s,
1H), 7.53 (d, 2H, J = 7.5 Hz), 6.87 (d, 2H, J = 7.4 Hz),
3.04 (m, 1H), 2.70 (s, 3H), 1.32 (q, 2H, J = 10.5 Hz), 0.96
(m, 2H); (M+H+) 326. Entry 16: 1H NMR (300 MHz,
CDCl3): d 8.61 (s, 1H), 7.64 (d, 2H, J = 7.1 Hz), 7.63 (s,
1H), 6.95 (d, 2H, J = 6.9 Hz), 3.85 (s, 3H), 3.13 (m, 1H),
2.71 (s, 3H), 1.35 (q, 2H, J = 10.8 Hz), 0.96 (m, 2H);
1
(M+H+) 340. Entry 17: H NMR (300 MHz, CDCl3): d
8.57 (s, 1H), 7.61 (s, 1H), 6.93 (s, 3H), 3.79 (s, 3H), 3.75 (s,
3H), 3.05 (m, 1H), 2.69 (s, 3H), 1.34 (q, 2H, J = 10.3 Hz),
0.97 (m, 2H); (M+H+) 370. Entry 18: 1H NMR (300
MHz, CD3OD): d 8.60 (s, 1H), 7.65 (s, 1H), 7.63 (d, 2H,
J = 8.1 Hz), 7.45 (d, 2H, J = 7.5 Hz), 3.03 (m, 1H), 2.67 (s,
3H), 1.34 (3, 11H), 0.93 (m, 2H); (M+H+) 366. Entry 19:
Trace observed via MS, no further data collected. Entry