Organic & Biomolecular Chemistry
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lected, concentrated on the rotary evaporator, and the crude 25 °C) δ = 7.82–7.80 (m, 2H), 7.52–7.36 (m, 8H), 7.31–7.28 (m,
product thus obtained was purified by use of column 2H), 7.25–7.22 (m, 1H), 3. 40 (b, 1H, NH), 3.26 (t, J = 7.0, 2H),
chromatography.
3-Methyl-N-octyl-1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4- 140.0, 138.8, 132.1, 132.0, 128.9, 128.7, 128.6, 128.5, 128.2,
2.84 (t, J = 7.0, 2H). 13C{1H} (125 MHz, CDCl3, 25 °C) δ = 144.3,
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amine (4a). Eluted with 5% EtOAc/hexanes. Physical aspect: 127.3, 126.4, 125.6, 121.2 (q, JC–F = 37), 120.9 (q, JC–F = 269,
yellow oil. Yield: 132 mg – 75%. NMR: 1H (500 MHz, CDCl3, CF3), 50.2, 36.6. HRMS (ESI-TOF): C24H21F3N3 (M + H) requires
25 °C) δ = 7.44–7.37 (m, 5H), 3.06 (t, J = 7.1, 2H), 2.31 (s, 3H), 408.1688/Found: 408.1685.
1.57 (qui, J = 7.2, 2H), 1.39–1.26 (m, 10H), 0.89 (t, J = 6.9, 3H).
N-(Furan-2-ylmethyl)-3-methyl-1-phenyl-5-(trifluoromethyl)-
13C{1H} (125 MHz, CDCl3, 25 °C) δ = 142.4, 140.0, 132.8, 128.9, 1H-pyrazol-4-amine (4g). Eluted with 10% EtOAc/hexanes.
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128.4, 125.5, 121.1 (q, JC–F = 269, CF3), 120.1 (q, JC–F = 36, Physical aspect: yellow oil. Yield: 72 mg – 45%. NMR: 1H
C-5), 49.2, 31.8, 30.5, 29.4, 29.2, 26.8, 22.6, 14.0, 12.0. HRMS (500 MHz, CDCl3, 25 °C) δ = 7.45–7.39 (m, 5H), 7.38 (dd, J =
(ESI-TOF): C19H27F3N3 (M + H) requires 354.2157/Found: 1.8, 0.7, 1H), 6.30 (dd, J = 3.1, 1.9, 1H), 6.17 (d, J = 3.1, 1H),
354.2135.
3-Methyl-N-octyl-1,3-diphenyl-5-(trifluoromethyl)-1H-pyrazol- CDCl3, 25 °C) δ = 152.6, 143.2, 142.2, 139.8, 131.1, 128.9,
4-amine (4b). Eluted with 5% EtOAc/hexanes. Physical aspect: 128.5, 125.6, 121.6 (q, JC–F = 37), 120.7 (q, JC–F = 269, CF3),
pale oil. Yield: 168 mg – 81%. NMR: 1H (500 MHz, CDCl3, 110.2, 107.4, 46.0, 11.5. HRMS (ESI-TOF): C16H14F3N3NaO
25 °C) δ = 7.89–7.88 (m, 2H), 7.52–7.43 (m, 7H), 7.39–7.35 (m, (M + Na) requires 344.0987/Found: 344.0982.
4.19 (s, 2H), 3.41 (b, 1H), 2.27 (s, 3H). 13C{1H} (125 MHz,
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1H), 2.95 (t, J = 7.1, 2H), 1.52 (qui, J = 7.1, 2H), 1.31–1.25 (m,
N-(Furan-2-ylmethyl)-1,3-diphenyl-5-(trifluoromethyl)-1H-
10H), 0.88 (t, J = 7.0, 3H). 13C{1H} (125 MHz, CDCl3, 25 °C) δ = pyrazol-4-amine (4h). Eluted with 10% EtOAc/hexanes. Physi-
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144.5, 140.0, 132.1, 132.0, 128.9, 128.7, 128.6, 128.2, 127.5, cal aspect: yellow oil. Yield: 81 mg – 42%. NMR: H (500 MHz,
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125.7, 121.4 (q, JC–F = 37), 120.9 (q, JC–F = 269, CF3), 49.5, CDCl3, 25 °C) δ = 7.93–7.90 (m, 2H), 7.50–7.42 (m, 7H),
31.7, 30.1, 29.3, 29.2, 26.7, 22.6, 14.0. HRMS (ESI-TOF): 7.40–7.37 (m, 1H), 7.34 (dd, J = 1.8, 0.8, 1H), 6.27 (dd, J = 3.1,
C24H28F3N3Na (M + Na) requires 438.2123/Found: 438.2129.
1.8, 1H), 6.07 (dd, J = 3.2, 0.7, 1H), 4.08 (s, 2H), 3.45 (b, 1H).
N-Benzyl-3-methyl-1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4- 13C{1H} (125 MHz, CDCl3, 25 °C) δ = 152.4, 144.6, 142.2, 139.8,
amine (4c). Eluted with 5% EtOAc/hexanes. Physical aspect: 132.0, 130.9, 128.9, 128.8, 128.7, 128.3, 127.4, 125.7, 122.2 (q,
pale oil. Yield: 116 mg – 70%. NMR: 1H (500 MHz, CDCl3, 2JC–F = 37), 120.7 (q, 1JC–F = 269, CF3), 110.1, 107.5, 45.6. HRMS
25 °C) δ = 7.46–7.39 (m, 5H), 7.37–7.34 (m, 4H), 7.33–7.29 (m, (ESI-TOF): C21H16F3N3NaO (M + Na) requires 406.1143/Found:
1H), 4.26 (s, 2H), 2.29 (s, 3H).
406.1143.
13C{1H} (125 MHz, CDCl3, 25 °C) δ = 142.8, 139.9, 139.2,
132.0, 128.9, 128.6, 128.5, 127.9, 127.5, 125.5, 124.1, 120.9 (q,
1JC–F = 269, CF3), 120.9 (q, JC–F = 37), 53.6, 11.8. HRMS
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Acknowledgements
(ESI-TOF): C18H17F3N3 (M + H) requires 332.1375/Found:
332.1365.
We are appreciative of the generous financial support of this
work from the Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq) and the Natural Sciences
and Engineering Research Council of Canada (NSERC
Canada).
N-Benzyl-1,3-diphenyl-5-(trifluoromethyl)-1H-pyrazol-4-amine
(4d). Eluted with 5% EtOAc/hexanes. Physical aspect: yellow
solid. Yield: 65 mg – 33%. Melting point: 56–58 °C. NMR: H
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(500 MHz, CDCl3, 25 °C) δ = 7.95–7.93 (m, 2H), 7.50–7.46 (m,
7H), 7.41–7.38 (m, 1H), 7.36–7.29 (m, 3H), 7.28–7.26 (m, 2H),
4.13 (s, 2H). 13C{1H} (125 MHz, CDCl3, 25 °C) δ = 145.1, 140.1,
138.7, 132.2, 129.2, 129.1, 128.9, 128.8, 128.6, 128.4, 127.9,
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127.8, 126.4, 126.0, 122.7 (q, JC–F = 38), 120.9 (q, JC–F = 269,
CF3), 53.8. HRMS (ESI-TOF): C23H19F3N3 (M + H) requires
394.1531/Found: 394.1532.
Notes and references
1 (a) J. Elguero, P. Goya, N. Jagerovic and A. M. S. Silva,
Targets Heterocycl. Syst., 2002, 6, 52; (b) T. Eicher,
S. Hauptmann and A. Speicher, The Chemistry of Hetero-
cycles, John Wiley & Sons, New York, 2nd edn, 2004;
(c) R. S. Keri, K. Chand, T. Ramakrishnappa and
B. M. Nagaraja, Arch. Pharm. Chem. Life Sci., 2015, 348, 1;
(d) C. Bissantz, B. Kuhn and M. Stahl, J. Med. Chem., 2010,
53, 5061.
2 (a) M. E. F. Braibante, G. Clar and M. A. P. Martins,
J. Heterocycl. Chem., 1993, 30, 1159; (b) L. P. Song,
Q. L. Chu and S. Z. Zhu, J. Fluorine Chem., 2001, 107, 107;
(c) H. G. Bonacorso, M. S. Correa, L. M. F. Porte,
E. P. Pittaluga, N. Zanatta and M. A. P. Martins, Tetrahedron
Lett., 2012, 53, 5488.
3-Methyl-N-phenethyl-1-phenyl-5-(trifluoromethyl)-1H-pyrazol-
4-amine (4e). Eluted with 5% EtOAc in hexanes. Physical
aspect: yellow oil. Yield: 117 mg – 68%. NMR: 1H (500 MHz,
CDCl3, 25 °C) δ = 7.46–7.39 (m, 5H), 7.35–7.32 (m, 2H),
7.26–7.24 (m, 3H), 3.38 (t, J = 7.1, 2H), 3.25 (NH, 1H), 2.91 (t,
J = 7.1, 2H), 2.26 (s, 3H). 13C{1H} (125 MHz, CDCl3, 25 °C) δ =
142.3, 139.9, 138.8, 132.0, 128.9, 128.7, 128.6, 128.4, 126.5,
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125.5, 120.9 (q, JC–F = 268, CF3), 120.3 (q, JC–F = 37), 50.1,
36.6, 11.9. HRMS (ESI-TOF): C19H19F3N3 (M + H) requires
346.1531/Found: 346.1523.
N-Phenethyl-1,3-diphenyl-5-(trifluoromethyl)-1H-pyrazol-4-
amine (4f). Eluted with 5% EtOAc/hexanes. Physical aspect:
yellow oil. Yield: 120 mg – 59%. NMR: 1H (500 MHz, CDCl3,
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