Paper
Organic & Biomolecular Chemistry
1.7 Hz, 2H), 8.11 (d, J = 7.8 Hz, 1H), 7.39 (dd, J = 8.1, 4.8 Hz,
1H); 13C NMR: (126 MHz, CD3OD) δC 151.3, 146.4, 138.9,
122.5, 120.6, C7 and three quaternary C’s do not appear; LCMS
tR = 1.28 min, m/z = 197 (M + H)+; purity (AUC) ≥ 95%; HRMS
(M + H)+ calculated for C11H9N4 = 197.0822, found = 197.0819.
2-(Pyridin-3-yl)-3H-imidazo[4,5-b]pyridine, 15k. Prepared by
general procedure D. Purification by flash column chromato-
graphy (0–8% MeOH in CH2Cl2) yielded product as a white
solid (20 mg, 38%); Lit m.p. 284 °C,30 observed m.p.
3 (a) S. De Ornellas, T. E. Storr, T. J. Williams,
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1
283–285 °C; H NMR: (500 MHz, DMSO-d6) δH 13.66 (bs, 1H),
5 T. C. Boorman and I. Larrosa, Chem. Soc. Rev., 2011, 40,
1910–1925.
9.34 (d, J = 1.8 Hz, 1H), 8.72 (dd, J = 4.9, 1.5 Hz, 1H), 8.61–8.53
(m, 1H), 8.46–8.38 (m, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.66 (dd,
J = 8.0, 4.9 Hz, 1H), 7.36 (dd, J = 8.1, 4.9 Hz, 1H); 13C NMR:
(126 MHz, CD3OD) δC 156.9, 152.1, 148.8, 145.8, 136.4, 127.5,
125.7, 120.2, C7 and two quaternary C’s do not appear; LCMS
(Method B) tR = 1.42 min, m/z = 197 (M + H)+; purity (AUC) ≥
95%; HRMS (M + H)+ calculated for C11H9N4 = 197.0822, found
= 197.0819; CHN Microanalysis calculated for C11H8N4 = C,
67.34; H, 4.11; N, 28.55%, observed = C, 67.29; H, 4.13;
N, 28.49%.
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M. A. Block, S. Cowen, A. M. Davies, E. Devereaux,
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D. Whitston, J. Wu, H.-J. Zhang, M. Zinda and C. Chuaqui,
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R. Feltell, J. Giraldes, S. D. Hiscock, S. Kim, S. Kovats,
B. Lagu, K. Lewry, A. Loo, Y. Lu, M. Luzzio, W. Maniara,
R. McMenamin, P. N. Mortenson, R. Benning, M. O’Reilly,
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A. J. A. Woolford, W. Wrona, M. Xu, F. Yang and S. Howard,
ACS Med. Chem. Lett., 2012, 3, 445–449; (d) D. Chen,
Y. Wang, Y. Ma, B. Xiong, J. Ai, Y. Chen, M. Geng and
2-(1-Methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine, 15l.
Prepared by general procedure D. Purification by flash column
chromatography (0–10% MeOH in CH2Cl2) yielded product as
an off-white solid (19 mg, 48%); Observed m.p. 274–278 °C;
1H NMR: (500 MHz, CD3OD) δH 8.32 (bs, 1H), 8.29 (s, 1H), 8.13
(s, 1H), 7.95 (dd, J = 8.0, 1.2 Hz, 1H), 7.29 (dd, J = 8.0, 4.9 Hz,
1H), 4.01 (s, 3H); 13C NMR: (126 MHz, CD3OD) δC 151.6, 149.1,
142.8, 137.9, 130.9, 122.4, 118.1, 112.5, two quaternary C’s do
not appear; LCMS tR = 1.14 min, m/z = 200 (M + H)+; purity
(AUC) ≥ 95%; HRMS (M + H)+ calculated for C10H10N5
=
200.0931, found = 200.0929; CHN Microanalysis calculated for
C10H9N5 = C, 60.29; H, 4.55; N, 35.16%, observed = C, 60.23; H,
4.59; N, 35.02%.
J.
Shen,
ChemMedChem,
2012,
7,
1057–1070;
(e) V. Bavetsias, J. M. Large, C. Sun, N. Bouloc,
M. Kosmopoulou, M. Matteucci, N. E. Wilsher, V. Martins,
J. h. Reynisson, B. Atrash, A. Faisal, F. Urban, M. Valenti,
A. de Haven Brandon, G. Box, F. I. Raynaud, P. Workman,
S. A. Eccles, R. Bayliss, J. Blagg, S. Linardopoulos and
E. McDonald, J. Med. Chem., 2010, 53, 5213–5228.
Acknowledgements
We thank Cancer Research UK (grants C309/A8274 (JM/VO),
C309/A11566 (JB/VB)) for funding. We also thank Dr Maggie
Liu, Dr Amin Mirza and Mr Meirion Richards assistance with
NMR and LCMS analysis.
7 M. Mader, A. de Dios, C. Shih, R. Bonjouklian, T. Li,
W. White, B. L. de Uralde, C. Sanchez-Martinez, M. del
Prado, C. Jaramillo, E. de Diego, L. M. Martin Cabrejas,
C. Dominguez, C. Montero, T. Shepherd, R. Dally,
J. E. Toth, A. Chatterjee, S. Pleite, J. Blanco-Urgoiti,
L. Perez, M. Barberis, M. J. Lorite, E. Jambrina, C. R. Nevill
Jr., P. A. Lee, R. C. Schultz, J. A. Wolos, L. C. Li,
R. M. Campbell and B. D. Anderson, Bioorg. Med. Chem.
Lett., 2008, 18, 179–183.
8 S.-C. Lee, H. T. Kim, C.-H. Park, D. Y. Lee, H.-J. Chang,
S. Park, J. M. Cho, S. Ro and Y.-G. Suh, Bioorg. Med. Chem.
Lett., 2012, 22, 4221–4224.
9 (a) R. P. Kale, M. U. Shaikh, G. R. Jadhav and C. H. Gill,
Tetrahedron Lett., 2009, 50, 1780–1782; (b) V. Bavetsias,
C. Sun, N. Bouloc, J. Reynisson, P. Workman,
S. Linardopoulos and E. McDonald, Bioorg. Med. Chem.
Lett., 2007, 17, 6567–6571; (c) S.-Y. Lin, Y. Isome, E. Stewart,
J.-F. Liu, D. Yohannes and L. Yu, Tetrahedron Lett., 2006,
47, 2883–2886.
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