LETTER
da Silva, L. L.; Romeiro, N. C.; Miranda, A. L. P.; Barreiro,
Synthesis of 3-Amino-2-arylimidazo[1,2-b]pyridazines
1743
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(22) Representative Procedure
tert-Butyl isocyanide (4a, 200 mg, 2.4 mmol), benzaldehyde
(5a, 233 mg, 2.2 mmol), and 3-amino-6-chloropyridazine (3,
260 mg, 2.0 mmo) are consecutively added to a solution of
NH4Cl (107 mg, 2.0 mmol) in MeOH (10 mL). The reaction
mixture is stirred for 16 h at r.t. Subsequently, the solvent
was removed in vacuo and the remainder taken up in EtOAc.
This organic layer was washed with brine and H2O, dried
over Na2SO4 and evaporated. The residue was purified either
by crystallization from Et2O or by chromatography on silica
gel, using cyclohexane–EtOAc (4:1) as eluent to deliver
3-tert-butylamino-6-chloro-2-phenylimidazo[1,2-b]pyrida-
zine as yellow crystals (6a, 500 mg, 1.7 mmol, 83%); mp
219–222 °C. 1H NMR (400 MHz, CDCl3): d = 1.13 (s, 9 H),
3.44 (br s, 1 H), 6.95 (d, 1 H), 7.32 (t, 1 H), 7.43 (t, 2 H), 7.80
(d, 1 H), 8.22 (d, 2 H) ppm. LC-MS: tR = 1.93 min, m/z = 301
[M + 1].
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Synth. Commun. 2010, 40, 111.
(24) Further Spectroscopic Data
Compound 6b: 1H NMR (400 MHz, CDCl3): d = 0.89 (t, 3
H), 1.38 (q, 2 H), 1.57 (q, 2 H), 3.15 (q, 2 H), 3.99 (t, 1 H),
6.85 (d, 1 H), 7.32 (t, 1 H), 7.44 (t, 2 H), 7.78 (d, 1 H), 8.03
(d, 2 H) ppm. LC-MS: tR = 2.05 min, m/z = 301 [M + 1].
Compound 6c: 1H NMR (400 MHz, CDCl3): d = 1.12–1.89
(m, 10 H), 3.22 (q, 1 H), 3.89 (d, 1 H), 6.87 (d, 1 H), 7.32 (t,
1 H), 7.44 (t, 2 H), 7.78 (d, 1 H), 8.10 (d, 2 H) ppm. LC-MS:
tR = 2.15 min, m/z = 327 [M + 1].
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I.; Banda, G.; Lentini, S. P.; Das, S.; Xu, Q.; Keats, J.; Wang,
F.; Wardwell, S.; Ning, Y.; Snodgrass, J. T.; Broudy, M. I.;
Russian, K.; Zhou, T.; Commodore, L.; Narasimhan, N. I.;
Mohemmad, Q. K.; Iuliucci, J.; Rivera, V. M.; Dalgarno, D.
C.; Sawyer, T. K.; Clackson, T.; Shakespeare, W. C. J. Med.
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Kawano, Y.; Fukui, H.; Ashida, Y.; Nagaya, H.
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K.; Kamei, T.; Gyoten, M.; Kawano, Y.; Ashida, Y.;
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K. H.; Edlin, C. D.; Bryans, J. S. Bioorg. Med. Chem. Lett.
2008, 18, 5294.
Compound 6d: 1H NMR (400 MHz, CDCl3): d = 1.11 (s, 6
H), 2.20 (s, 3 H), 2.73 (s, 2 H), 3.96 (br s, 1 H), 6.96 (d, 1 H),
7.33 (t, 1 H), 7.42 (t, 2 H), 7.80 (d, 1 H), 8.21 (d, 2 H) ppm.
LC-MS: tR = 2.04 min, m/z = 347 [M + 1].
Compound 6e: 1H NMR (400 MHz, CDCl3): d = 1.03 (s, 6
H), 1.10 (s, 9 H), 1.18 (s, 2 H), 3.56 (br s, 1 H), 6.91 (d, 1 H),
7.31 (t, 1 H), 7.42 (t, 2 H), 7.78 (d, 1 H), 8.17 (d, 2 H) ppm.
LC-MS: tR = 2.32 min, m/z = 357 [M + 1].
Compound 6f: 1H NMR (400 MHz, CDCl3): d = 5.88 (br s,
1 H), 6.55 (d, 1 H), 6.64 (s, 1 H), 6.72–6.79 (m, 2 H), 7.05
(d, 1 H), 7.29–7.56 (m, 4 H), 7.91 (d, 1 H), 8.10 (d, 2 H) ppm.
LC-MS: tR = 1.89 min, m/z = 361 [M + 1].
Compound 6g: 1H NMR (400 MHz, CDCl3): d = 2.01 (s, 6
H), 5.69 (br s, 1 H), 6.81–6.93 (m, 4 H), 7.14–7.20 (m, 3 H),
7.58 (dd, 2 H), 7.82 (d, 1 H) ppm. LC-MS: tR = 2.03 min,
m/z = 349 [M + 1].
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del Prado, M.; Lopez, J.; Rubio, A.; Heinz, B. A. J. Med.
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(19) Russell, M. G. N.; Carling, R. W.; Street, L. J.; Hallett, D. J.;
Goodacre, S.; Mezzogori, E.; Reader, M.; Cook, S. M.;
Bromidge, F. A.; Newman, R.; Smith, A. J.; Wafford, K. A.;
Marshall, G. R.; Reynolds, D. S.; Dias, R.; Ferris, P.;
Stanley, J.; Lincoln, R.; Tye, S. J.; Sheppard, W. F. A.;
Compound 6h: 1H NMR (400 MHz, CDCl3): d = 4.30–4.39
(m, 3 H), 6.87 (d, 1 H), 7.19–7.36 (m, 6 H), 7.47 (t, 2 H), 7.78
(d, 1 H), 8.01 (d, 2 H) ppm. LC-MS: tR = 1.98 min, m/z = 335
[M + 1].
Compound 6i: 1H NMR (400 MHz, CDCl3): d = 1.11 (s, 9
H), 3.46 (br s, 1 H), 6.99 (d, 1 H), 7.52–7.83 (m, 4 H), 8.47
(d, 1 H), 8.66 (d, 1 H) ppm. LC-MS: tR = 2.19 min, m/z = 369
[M + 1].
Synlett 2011, No. 12, 1740–1744 © Thieme Stuttgart · New York