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T. A. BAKKA AND O. R. GAUTUN
MeOH/NH4OH) the reaction mixture was cooled down to room temperature. Furthermore,
depending on whether the product precipitated out or not, the following was done:
A) If the product was precipitated by cooling the reaction mixture to room temperature,
the supernatant was removed and the precipitate was washed with MeCN and dried
under reduced pressure.
B) If the product was not precipitated by cooling the reaction mixture to room tempera-
ture, Et2O was added to induce precipitation. The precipitate was then washed with
Et2O and dried under reduced pressure.
Synthesis of 2c
1. General procedure B leads to 2c as a light yellow sticky wax (137 mg, 0.69 mmol, 84%
yield).
2. General procedure B(a) leads to 2c as an off-white solid (13 g, 65 mmol, 93% yield).
1H NMR (400 MHz, d4-MeOH): δ ¼ 7.36–7.22 (m, 5H, Ph-), 3.46 (t, 2H, J ¼ 7.1 Hz,
-NH-CH2-), 2.88 (t, 2H, J ¼ 7.1 Hz, Ph-CH2-) ppm. 13C NMR (100 MHz, d4-MeOH):
=
157.1 (NH-C NH), 137.9 (CH-C-CH), 128.4 (2xCH), 128.3 (2xCH), 126.4 (CH), 42.3
(-CH2-NH-), 34.5 (C-CH2-) ppm. Spectra is highly similar to spectra of the sulfate salt
in D2O reported in a patent by the University of Strathclyde.[14]
Procedure B(a): Preparative scale workup
The reaction mixture was partially evaporated and added to Et2O (200 mL). The ether
phase was decanted and the residual oil was washed with Et2O (3 � 200 mL), before it
was added one last portion of Et2O (200 mL) and left for 48 h. The hard crystalline precipi-
tate was then crushed and stirred with Et2O (3 � 100 mL) for 10 min each time. Decanting
and drying afforded 2c as an off-white solid.
References
[1] Katritzky, A. R.; Rogovoy, B. V. Arkivoc 2005, 4, 49–87.
[2] Bernatowicz, M. S.; Wu, Y.; Matsueda, G. R. J. Org. Chem. 1992, 57, 2497–2502.
[3] Davis, T. L. Org. Synth. 1927, 7, 46–49.
[4] Cosand, W. L.; Merrifield, R. B. Proc. Natl. Acad. Sci. U. S. A. 1977, 74, 2771–2775.
[5] Kämpf, A. Ber. Dtsch. Chem. Ges. 1904, 37, 1681–1684.
[6] Arndt, F.; Rosenau, B. Ber. Dtsch. Chem. Ges. 1917, 50, 1248–1261.
[7] Braun, C. E. J. Am. Chem. Soc. 1933, 55, 1280–1284.
[8] Bannard, R. A. B.; Casselman, A. A.; Cockburn, W. F.; Brown, G. M. Can. J. Chem. 1958, 36,
1541–1549.
[9] Reaxys database reaction search, August 2016.
[10] Bennett, C. N. H.; Kurt, D.; Harrison, S. D.; Longo, K. A.; MacDougald, O. A.; Wagman, A. S.
GSK-3 inhibitors, US Patent No. US20050054663, 2005.
[11] Amgen Inc, Aminopyrimidine compounds and methods of use, Patent No/ WO20060661172
A1, 2006.
[12] Nuss, J. M. H.; Stephen, D.; Ring, D. B.; Boyce, R. S.; Johnson, K.; Pfister, K. B.; Ramurthy, S.;
Seely, L.; Wagman, A. S.; Desai, M.; Levine, B. H. Inhibitors of glycogen synthase kinase 3, US
Patent Np. US20020156087 A1, 2002.
[13] Nielsen, M. C.; Larsen, A. F.; Abdikadir, F. H.; Ulven, T. Eur. J. Med. Chem. 2014, 72, 119–126.
[14] Waigh, R. D.; Harvey, A. L.; Mooney, M. H.; Coxon, G. Weight reducing compounds, Patent
No. WO2009087395, 2009.