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-I-
References and notes
+SCN
R1
NH4SCN +
NCS I
I
I
-NH4I
R1
1. (a) Kaufman, H. P.; Weber, E. Arch. Pharm. 1929, 267, 201; (b) Kaufmann, H. P.
Ber. 1929, 62, 390; (c) Kaufmann, H. P.; Kuchler, K. Ber. 1934, 67, 944; (d)
Kaufmann, H. P.; Schulz, P. Arch. Pharm. 1935, 31, 273.
R1
+SCN
NH2
H
SCN
SCN
2. Maggiolo, A.; Hitchings, G. H. J. Am. Chem. Soc. 1951, 73, 4226.
3. Baker, J. A.; Chatfield, P. V. J. Chem. Soc. (C) 1970, 2478.
4. Aoyama, T.; Murata, S.; Arai, I.; Araki, N.; Takido, T.; Suzukib, Y.; Kodomari, M.
Tetrahedron 2006, 62, 3201.
N
N
N
N
-H+
N
R
R
NH2
N
R
NH2
5.
A ) showed some thiocyanates of
recent search on the web (SciFinderÒ
Scheme 4. Proposed mechanism for the thiocyanation.
aminopyrimidine derivatives unfortunately in most of the cases there were
not bibliographic information available.
6. (a) Insuasty, B.; García, A.; Quiroga, J.; Abonia, R.; Nogueras, M.; Cobo, J. Eur. J.
Med. Chem. 2010, 45, 2841; (b) Quiroga, J.; Trilleras, J.; Insuasty, B.; Abonía, R.;
Nogueras, M.; Marchal, A.; Cobo, J. Tetrahedron Lett. 2010, 51, 1107; (c)
Rodríguez, R.; Nogueras, M.; Cobo, J.; Glidewell, C. Acta Crystallogr. 2009, C65,
o111; (d) Rodríguez, R.; Nogueras, M.; Cobo, J.; Glidewell, C. Acta Crystallogr.
2009, C65, o441; (e) Quiroga, J.; Trilleras, J.; Gálvez, J.; Insuasty, B.; Abonía, R.;
Nogueras, M.; Cobo, J. Tetrahedron Lett. 2009, 50, 6404; (f) Cobo, J.; Nogueras,
M.; Low, J. N.; Rodríguez, R. Tetrahedron Lett. 2008, 49, 7272; (g) Rodríguez, R.;
Cobo, J.; Nogueras, M.; Low, J. N.; Glidewell, C. Acta Crystallogr. 2008, C64, o376;
(h) Rodríguez, R.; Cobo, J.; Nogueras, M.; Low, J. N.; Glidewell, C. Acta
Crystallogr. 2008, C64, o392; (i) Insuasty, B.; Orozco, F.; Lizarazo, C.; Quiroga,
J.; Abonia, R.; Hursthouse, M.; Nogueras, M.; Cobo, J. Bioorg. Med. Chem. 2008,
16, 8492; (j) Quiroga, J.; Trilleras, J.; Gálvez, J.; Insuasty, B.; Abonía, R.;
Nogueras, M.; Cobo, J.; Marchal, A. Tetrahedron Lett. 2008, 49, 5672; (k)
Rodríguez, R.; Cobo, J.; Nogueras, M.; Low, J. N.; Glidewell, C. Acta Crystallogr.
2007, C63, o697.
7. General procedure for thiocyanation of aminopyrimidine derivatives: Ammonium
thiocyanate (3 mmol) and iodine (1.0 mmol) are added at room temperature to
a stirred solution of the corresponding aminopyrimidine derivative (1.0 mmol)
in methanol (10 mL). After completion of the reaction (TLC control), a sodium
thiosulfate solution [20% (w/v)] is added to destroy the remaining iodine. The
solid formed is filtered off, washed with water, and recrystallized from a
methanol/water solution. For more details see Table 1 and Supplementary data.
8. Okafor, C. O. J. Heterocycl. Chem. 1980, 17, 1587.
ing several thiocyanates of aminopyrimidine derivatives, which
have been fully characterized, and show promising bioactivities.
In addition, these compounds constitute a valuable precursor to
potential bioactive fused pyrimidine derivatives bearing a sulfur
atom in the heterocyclic nucleus.
Acknowledgments
R.R. thanks Fundación Banco de la República (project reference
2575) for the financial support to this investigation. J.C. and M.N.
thank the Consejería de Economía, Innovación y Ciencia (Junta de
Andalucía, Spain), the Universidad de Jaén and Ministerio de Cien-
cia e Innovación (project reference SAF2008-04685-C02-02) for
financial support. Authors thank Christopher Thompson for
reviewing the present manuscript.
Supplementary data
9. At the same time the typical signal for a tertiary carbon at C-5 position
disappears in DEPT-135 spectra.
10. For details see Supplementary data.
11. Jang, M. Y.; Jonghe, S.; Segers, K.; Anné, J.; Herdewijn, P. Bioorg. Med. Chem.
2011, 19, 702.
Supplementary data associated with this article can be found, in