Y. Sandulenko et al. / Tetrahedron Letters 49 (2008) 5990–5993
5993
9. Blackburn, C.; Guan, B. Tetrahedron Lett. 2000, 41, 1495–1500.
toluene (1.5 mL). The vial was flushed with nitrogen and sealed
10. For key reviews on the Buchwald–Hartwig reaction see: (a) Buchwald, S. L.;
Mauger, C.; Mignani, G.; Scholz, U. Adv. Synth. Catal. 2006, 348, 23–39; (b) Yang,
B. H.; Buchwald, S. L. J. Organomet. Chem. 1999, 576, 125–146; (c) Wolfe, J. P.;
Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805–
818.
with a septum top. The catalyst solution was prepared by mixing
14
Pd(OAc)2
(0.008 mmol) and BINAP (0.016 mmol) in toluene
(0.5 mL). After shaking at 80 °C for 2 min, the catalyst solution
was added to the reaction vial via a syringe. The mixture was
heated at 100 °C under vigorous stirring for 16 h after which the
mixture was cooled to rt and the solvent was removed in vacuo.
The residue was partitioned between ethyl acetate (3 mL) and
water (2 mL). The organic layer was separated, dried over anhy-
drous Na2SO4, filtered, and concentrated to give the crude product.
The latter was purified by column chromatography on silica gel
using an appropriate gradient of ethyl acetate in dichloromethane
as eluent.
11. (a) Walborsky, H. M.; Niznik, G. E. J. Am. Chem. Soc. 1969, 91, 7778–7780; (b)
Walborsky, H. M.; Niznik, G. E. J. Org. Chem. 1972, 37, 187–191.
12. Under traditional conditions (methanol, Brønsted or Lewis acid catalyst),
the Groebke–Blackburn reaction has been noted to lead also to regioisomeric
2-amino-3-phenylimidazo[1,2-a]azines: (a) Mandair, G. S.; Light, M.; Russell,
A.; Hursthouse, M.; Bradley, M. Tetrahedron Lett. 2002, 43, 4267–4269; (b)
Ref. 6e.
13. Compound 3b: Brown sticky solid; 1H NMR (300 MHz, DMSO-d6) d 8.67 (d,
J = 4.8 Hz, 2H), 8.43 (d, J = 4.3 Hz, 1H), 8.27 and 8.51 (m, 1H), 7.90–8.00 (m, 3H),
7.47–7.60 (m, 1H), 7.38–7.46 (m, 2H), 7.29 (t, J = 4.8 Hz, 1H), 6.96 (t, J = 4.8 Hz,
1H); 13C NMR (75 Hz, DMSO-d6) d 159.9, 159.1, 159.0, 138.0, 126.6, 130.1,
129.3, 129.0, 127.2, 125.8, 118.0, 116.9, 114.1, 112.9; LCMS (M+H+) 288; calcd
for C17H13N5: C, 71.07; H, 4.56; N, 24.37. Found: C, 70.98; H, 4.49; N, 24.31.
Compound 3c: Sticky solid; 1H NMR (300 MHz, DMSO-d6) d 9.29 (s, 1H), 8.36
(d, J = 6.8 Hz, 1H), 8.03 (d, J = 8.9 Hz, 1H), 7.88–7.94 (m, 3H), 7.81 (d, J = 8.7 Hz,
2H), 7.51 (m, 3H), 7.40 (t, J = 6.8 Hz, 1H), 6.80 (d, J = 8.4 Hz, 2H), 2.44 (s, 3H);
13C NMR (75 Hz, DMSO-d6) d 195.9, 149.1, 138.9, 132.3, 131.1, 130.7, 129.8,
129.2, 128.9, 127.6, 126.9, 124.7, 119.1, 116.5, 113.7, 113.1, 26.2; LCMS (M+H+)
328; calcd for C21H17N3O: C, 77.04; H, 5.23; N, 12.83. Found: C, 77.98; H, 5.22;
N, 12.79.
References and notes
1. Groebke, K.; Weber, L.; Mehlin, F. Synlett 1998, 661–663.
2. Blackburn, C.; Guan, B.; Fleming, P.; Shiosaki, K.; Tsai, S. Tetrahedron Lett. 1998,
39, 3635–3638.
3. Bienaymé, H.; Bouzid, K. Angew. Chem., Int. Ed. 1998, 37, 2234–2237.
4. Krasavin, M.; Tsirulnikov, S.; Nikulnikov, M.; Kysil, V.; Ivachtchenko, A.
Compound 3h: Sticky brown solid; 1H NMR (300 MHz, DMSO-d6) d 10.79 (s,
1H), 8.49 (unresolved d, 1H), 8.30 (t, J = 8.5 Hz, 1H), 8.26 (unresolved d, 1H),
7.84–7.91 (m, 3H), 7.63 (t, J = 8.5 Hz, 1H), 7.39–7.52 (m, 4H), 7.19 (t, J = 6.6 Hz,
1H), 6.60 (d, J = 7.6 Hz, 1H); 13C NMR (75 Hz, DMSO-d6) d 158.5, 158.3, 158.0,
157.0, 145.9, 144.6, 141.5, 135.6, 130.5, 129.1, 128.7, 126.7, 123.9, 116.0, 114.8,
114.6; LCMS (M+H+) 287; calcd for C18H14N4: C, 75.51; H, 4.93; N, 19.57.
Found: C, 75.58; H, 4.94; N, 19.62.
5. Examples of recent patents and patent applications related to the Groebke–
Blackburn reaction: (a) Klein, M.; Gericke, R.; Beier, N.; Cezanne, B.; Tsaklakidis,
C.; Mederski, W. German Patent DE 102006048728, 2008; Chem. Abstr. 2008,
148, 475292; (b) Muci, A.; Finer, J. T.; Morgan, B. P.; Russell, A. J.; Morgans, D. J.,
Jr. PCT Int. Appl. WO 2008016648 A2, 2008; Chem. Abstr. 2008, 148, 215052; (c)
Mederski, W.; Beier, N.; Cezanne, B.; Gericke, R.; Klein, M.; Tsaklakidis, C. PCT
Int. Appl. WO 2007147478 A1, 2007; Chem. Abstr. 2008, 148, 100605; (d)
Thormann, M. German Patent DE 102005019181, 2006; Chem. Abstr. 2006, 145,
471525.
6. For recent examples of isocyanide-based reactions of 2-aminoazines and
-azoles see: (a) Rousseau, A. L.; Matlaba, P.; Parkinson, C. J. Tetrahedron Lett.
2007, 48, 4079–4082; (b) Shaabani, A.; Soleimani, E.; Maleki, A. Tetrahedron
Lett. 2006, 47, 3031–3034; (c) DiMauro, E. F.; Kennedy, J. M. J. Org. Chem. 2007,
72, 1013–1016; (d) Kercher, T.; Rao, C.; Bencsik, J. R.; Josey, J. A. J. Comb. Chem.
2007, 9, 1177–1187; (e) Carballares, S.; Cifuentes, M. M.; Stephenson, G. A.
Tetrahedron Lett. 2007, 48, 2041–2045; (f) Umkehrer, M.; Ross, G.; Jäger, N.;
Burdack, C.; Kolb, J.; Hu, H.; Alvim-Gaston, M.; Hulme, C. Tetrahedron Lett. 2007,
48, 2213–2216; (g) Shaabani, A.; Maleki, A.; Moghimi, R. J.; Soleimani, E. Chem.
Pharm. Bull. 2007, 55, 957–958; (h) Adib, M.; Mahdavi, M.; Noghani, M. A.;
Mirzaei, P. Tetrahedron Lett. 2007, 48, 7263–7265.
Compound 3o: Off-white solid, mp = 169–171 °C (decomp.); 1H NMR
(300 MHz, DMSO-d6) d 9.08 (d, J = 1.0 Hz, 1H), 8.24 (d, J = 1.0 Hz, 1H), 7.96–
8.06 (m, 5H), 7.88 (d, J = 4.0 Hz, 1H), 7.43 (d, J = 7.0 Hz, 2H), 7.35 (d, J = 7.0 Hz,
1H), 6.30 (br s, NH + bound H2O); 13C NMR (75 Hz, DMSO-d6) d 158.3, 157.8,
152.9, 142.3, 141.8, 140.2, 137.3, 135.0, 133.1, 128.6, 128.4, 128.2, 127.0,
116.9; LCMS (M+H+) 289; calcd for C16H12N6: C, 66.66; H, 4.20; N, 29.15.
Found: C, 66.72; H, 4.25; N, 29.21.
Compound 3p: Off-white solid, mp = 137–139 °C (decomp.); 1H NMR
(300 MHz, DMSO-d6) d 9.10 (s, 1H), 8.37 (d, J = 4.0 Hz, 2H), 8.05 (d, J = 1.0 Hz,
1H), 8.03 (m, 2H), 7.89 (d, J = 4.0 Hz, 1H), 7.43 (t, J = 7.0 Hz, 2H), 7.34 (dd,
J = 1.0, 7.0 Hz, 1H), 6.85 (t, J = 4.0 Hz, 1H), 6.80 (br s, NH + bound H2O); 13C NMR
(75 Hz, DMSO-d6) d 161.1, 158.5, 158.4, 157.9, 142.1, 140.2, 137.0, 132.8, 128.9,
128.2, 127.0, 119.4, 116.9, 113.3; LCMS (M+H+) 289; calcd for C16H12N6: C,
66.66; H, 4.20; N, 29.15. Found: C, 66.65; H, 4.21; N, 29.17.
7. Parchinsky, V. Z.; Shuvalova, O.; Ushakova, O.; Kravchenko, D. V.; Krasavin, M.
Tetrahedron Lett. 2006, 47, 947–951.
8. Krasavin, M.; Parchinsky, V. Synlett 2008, 645–648.
14. In a control experiment, arylation of 1a was attempted with 2-chloropyrazine
in the absence of the palladium catalyst which resulted in virtually no
conversion (as evidenced by LCMS analysis of the reaction mixture).