2886
S.-Y. Lin et al. / Tetrahedron Letters 47 (2006) 2883–2886
40, Part 2; Chapter 10; According to Evans, a privileged
245 lmol) were charged. The sealed vial was irradiated
in the microwave for 10 min at 220 °C. The pressure
reading at this temperature was 8.1 bar. After cooling, the
reaction mixture was concentrated in vacuo and the
residue was purified by preparative TLC (CH2Cl2/MeOH,
20/1) to give the desired product 4 (Table 2, entry 5):
2-propyl-1H-benzimidazole; 27.5 mg (86%); 1H NMR
(CDCl3, 400 MHz) d 0.98 (t, J = 7.6 Hz, 3H), 1.91 (m,
2H), 2.96 (t, J = 7.6 Hz, 2H), 7.21–7.60 (dd, J = 3.2,
6.0 Hz, 2H), 7.56 (dd, J = 3.2, 6.0 Hz, 2H), 10.9 (br s, 1H);
13C NMR (CDCl3, 100 MHz) d 14.2, 22.1, 31.6, 115.0,
122.5, 138.9, 155.9; HRMS calcd for (C17H16N2O2+H)
161.1073, found 161.1076.
structure is ‘a single molecular framework able to provide
ligands for diverse receptors’, see: (b) Evans, B. E.; Rittle,
K. E.; Bock, M. G.; DiPardo, R. M.; Freidinger, R. M.;
Whitter, W. L.; Lundell, G. F.; Veber, D. F.; Anderson, P.
S.; Chang, R. S. L.; Lotti, V. J.; Cerino, D. J.; Chen, T. B.;
Kling, P. J.; Kunkel, K. A.; Springer, J. P.; Hirshfield, J. J.
Med. Chem. 1988, 31, 2235.
5. Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev.
2003, 103, 893, and references cited therein.
6. Yang, D.; Fokas, D.; Li, J.; Yu, L.; Baldino, C. M.
Synthesis 2005, 47.
7. For reviews on the chemistry of benzimidazoles, see: (a)
Wright, J. B. Chem. Rev. 1951, 48, 397; (b) Preston, P. N.
Chem. Rev. 1974, 74, 279; (c) Gray, D. N. J. Heterocycl.
Chem. 1970, 7, 947; (d) Hudkins, R. L. Heterocycles 1995,
41, 1045; (e) Brain, C. T.; Brunton, S. A. Tetrahedron Lett.
2002, 43, 1893; (f) Brain, C. T.; Steer, J. T. J. Org. Chem.
2003, 68, 6814; (g) Howarth, J.; Hanlon, K. Tetrahedron
Lett. 2001, 42, 751; (h) Hendrickson, J. B.; Hussoin, S. M.
J. Org. Chem. 1989, 54, 1144.
8. General reaction procedure for the synthesis of benz-
imidazoles from acids and diamines are described in Table
2: In a conical-bottomed Smith Process vial, 0.5 mL of
butyric acid in anhydrous pyridine (0.4 M, 200 lmol),
0.5 mL of 1,2-phenylenediamine in anhydrous pyridine
(0.4 M, 200 lmol), and triphenyl phosphite (70 lL,
9. 1H NMR (CD3OD, 400 MHz) d 1.37–1.43 (m, 2H), 1.51–
1.57 (m, 2H), 1.85–1.88 (m, 2H), 2.24–2.27 (m, 2H), 3.18–
3.21 (m, 2H), 7.16 (dd, J = 4.0, 4.8 Hz, 1H), 7.64 (dd
J = 3.6, 1.2 Hz, 1H), 7.68 (dd, J = 4.8, 1.2 Hz, 1H); 13C
NMR (CD3OD, 100 MHz) d 26.3, 31.8, 70.2, 129.5, 131.6,
132.3, 133.2, 163.8; HRMS calcd for (C11H14N2S+H)
207.0951, found 207.0952.
10. We employed a Biotage Smith SynthesizerTM integrated
into the ArQule AMAPTM high-throughput chemistry
platform.
11. (a) Kyranos, J. N.; Cai, H.; Zhang, B.; Goetzinger, W. K.
Curr. Opin. Drug Discovery Dev. 2001, 4, 719; (b)
Goetzinger, W.; Zhang, X.; Bi, G.; Towle, M.; Cherrak,
D.; Kyranos, J. N. Int. J. Mass. Spectrom. 2004, 238, 153.