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Hernandez et al.
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J = 9.0 Hz), 127.7, 129.1 (d, J = 9.0 Hz), 132.0, 136.5, 140.8,
147.9, 162.4 (d, J = 245.9 Hz); IR 1619 cm-1; HRMS calcd for
C19H17FN2 292.1376, found 292.1368.
124.7, 125.8, 128.3, 129.2, 134.1, 137.3, 141.0, 159.5; IR 1621
cm-1; HRMS calcd for C16H12N2O 248.0950, found 248.0939.
5,6-Dimethoxypyrazolo[1,5-f ]phenanthridine (1q): 35%, white
needles, mp 168-171 °C (MeOH); 1H NMR (250 MHz, CDCl3) δ
3.98 (3H, s), 4.00 (3H, s), 6.74 (1H, d, J = 1.6 Hz), 7.18 (1H, s),
7.36-7.42 (1H, m), 7.50 (1H, s), 7.51-7.57 (1H, m), 7.92 (1H, d,
J = 1.6 Hz), 8.06-8.09 (1H, m), 8.47-8.51 (1H, m); 13C NMR
(63 MHz, CDCl3) δ 55.8, 55.9, 97.7, 103.7, 104.9 116.1, 117.8,
120.5 120.8, 122.6, 124.6, 128.0, 133.0, 137.0, 140.7, 149.6; IR
1617 cm-1; HRMS calcd for C17H14N2O2 278.1055, found
278.1055.
9-Trifluoromethyl-6-fluoropyrazolo[1,5-f ]phenanthridine (1m):
1
50%, white powder. mp 138-141 °C (EtOH); H NMR (250
MHz, CDCl3) δ 6.99 (1H, d, J = 2.0 Hz), 7.35-7.42 (1H, m),
7.92 (1H, dd, J = 8.7, 1.6 Hz), 8.02-8.13 (3H, m), 8.53 (1H, s),
8.71 (1H, d, J = 8.7 Hz); 13C NMR (63 MHz, CDCl3) δ 99.6,
109.0 (d, J = 23.3 Hz), 117.2, 117.3 (d, J = 23.3 Hz), 120.3 (d,
J = 3.6 Hz), 121.0 (q, J = 3.6 Hz), 126.3, 126.7 (d, J = 9.0 Hz),
127.9 (d, J = 9.0 Hz), 135.8, 137.2, 142.1, 162.6 (d, J = 249.5
Hz); IR 1612 cm-1; HRMS calcd for C16H8F4N2 304.0624,
found 304.0622.
6,7-Dimethoxypyrazolo[1,5-f ]phenanthridine (1q0): 35%, white
needles, mp 134-136 °C (MeOH); 1H NMR (250 MHz, CDCl3)
δ 3.95 (3H, s), 4.00 (3H, s), 6.86 (1H, d, J = 2.0 Hz), 7.22 (1H, d,
J = 8.7 Hz), 7.48 (1H, tdd, J = 8.3, 1.2 Hz), 7.65 (1H, tdd, J =
8.3, 1.2 Hz), 7.82 (1H, d, J = 8.7 Hz), 7.93 (1H, d, J = 2.0 Hz),
Synthesis of Pyrazolo[1,5-f ]phenanthridines 1 through Hetero-
geneous Catalytic Direct Arylation. General Procedure. Dry
degassed DMF (6 mL) was added to an oven-dried reaction
flask charged with 1,5-diarylpyrazol 2 (0.3 mmol) K2CO3
(1.7 mmol), and FibreCat 1000-D7 (0.03 mmol of Pd) at room
temperature under argon. The stirred suspension was heated to
110 °C for 3 days. After cooling, the mixture was diluted with
CH2Cl2, (30 mL) and filtered. The solvent was evaporated under
reduced pressure and the so-obtained residue was purified by
flash chromatography on silica gel with EtOAc/hexanes as
eluent.
Synthesis of Pyrazolo[1,5-f ]phenanthridines 1 through Radical
Coupling. General procedure. A solution of TTMSS (0.2 mmol)
and AIBN (0.5 mmol) in dry degassed toluene (4.5 mL) was
added dropwise to a solution of 1,5-diarylpyrazole 2 (0.5 mmol)
in the same solvent (6 mL). The mixture was heated at reflux for
7 h. After cooling, the solvent was evaporated under reduced
pressure and the so-obtained residue was purified by flash
chromatography on silica gel with EtOAc/hexanes as eluent.
5-Methoxypyrazolo[1,5-f ]phenanthridine (1n): 24%, white
needles, mp 111-114 °C (MeOH); 1H NMR (250 MHz, CDCl3)
δ 3.97 (3H, s), 6.96 (1H, d, J = 1.6 Hz), 7.19 (1H, dd, J = 8.7, 2.4
Hz), 7.44-7.50 (2H, m), 7.57-7.63 (1H, m), 7.99 (1H, d, J = 1.6
Hz), 8.26-8.30 (2H, m), 8.56-8.59 (1H, m); 13C NMR (63
MHz, CDCl3) δ 55.5, 99.2, 106.4, 116.2, 116.9, 120,4. 121.3,
122.8, 124.4, 125.0, 125.2, 128.1, 133.0, 137.2, 140.8, 159.4; IR
1619 cm-1; HRMS calcd for C16H12N2O 248.0950, found
248.0944.
8.62 (1H, dd, J = 8.3, 1.2 Hz), 9.38 (1H, dd, J = 8.3, 1.2 Hz); 13
C
NMR (63 MHz, CDCl3) δ 56.2, 59.9, 98.3, 113.1, 115.9, 118.9,
120.6, 120.8, 121.2, 125.1, 128.5, 129.1, 134.1, 137.2, 141.0, 147.4,
153.1; IR 1612 cm-1; HRMS calcd for C17H14N2O2 278.1055,
found 278.1058.
10-Methylpyrazolo[1,5-f ]phenanthridine (1r): 76%, white
powder, mp 87-90 °C (MeOH); 1H NMR (250 MHz, CDCl3)
δ 2.52 (3H, s), 6.92 (1H, d, J = 2.0 Hz), 7.19-7.22 (1H, m),
7.44-7.53 (2H, m), 7.94-7.98 (1H, m), 7.96 (1H, d, J = 2.0 Hz),
8.12 (1H, d, J = 8.3 Hz), 8.19-8.23 (1H, m), 8.35 (1H, s); 13
C
NMR (63 MHz, CDCl3) δ 21.6, 99.0, 116.2, 118.7, 122.4, 123.1,
123.4, 124.2, 126.2, 126.8, 127.5, 128.0, 133.7, 137.4, 139.6,
140.8; IR 1625 cm-1; HRMS calcd for C16H12N2 232.1000,
found 232.1006.
6,10-Dimethylpyrazolo[1,5-f ]phenanthridine (1s): 78%, white
powder, mp 120-123 °C (MeOH); 1H NMR (250 MHz, CDCl3)
δ 2.48 (3H, s), 2.52 (3H, s), 6.86 (1H, d, J = 2.4 Hz), 7.20 (1H,
dd, J = 8.3, 1.2 Hz), 7.24-7.27 (1H, m), 7.81 (1H, d, J = 7.9
Hz), 7.94 (1H, d, J = 2.0 Hz), 7.97 (1H, s), 8.10 (1H, d, J = 8.2
Hz), 8.33 (1H, s); 13C NMR (63 MHz, CDCl3) δ 21.5, 21.8, 98.5,
116.1, 118.6, 121.0, 122.3, 123.0, 124.1, 126.0, 126.7, 128.7,
133.7, 137.5, 137.9, 139.4, 140.7; IR 1619 cm-1; HRMS calcd
for C17H14N2 246.1157, found 246.1147.
6-Methyl-10-trifluoromethylpyrazolo[1,5-f ]phenanthridine (1t):
74% white powder, mp 195-199 °C (MeOH); 1H NMR:
(250 MHz, CDCl3) δ 2.57 (3H, s), 6.94 (1H, d, J = 2.0 Hz),
7.43-7.46 (1H, m), 7.66-7.69 (1H, m), 7.92-7.95 (1H, m), 7.99
(1H, d, J = 2.0 Hz), 8.12 (1H, s), 8.42-8.45 (1H, m), 8.54 (1H, s);
13C NMR (63 MHz, CDCl3) δ 21.9, 99.2, 113.9, 121.0 (q, J = 3.6
Hz), 122.1, 123.1, 123.7, 123.8 (q, J= 271.1 Hz), 124.0, 124.4, 125.6,
130.6, 130.7 (q, J = 32.3 Hz), 133.6, 137.6, 138.6, 141.5; IR
1619 cm-1;HRMScalcdforC17H11F3N2 300.0874, found 300.0874.
7-Methoxypyrazolo[1,5-f ]phenanthridine (1n0): 24%, white
needles, mp 125-127 °C (MeOH); 1H NMR (250 MHz, CDCl3)
δ 4.08 (3H, s), 6.96 (1H, d, J = 2.0 Hz), 7.08-7.11 (1H, m),
7.43-7.52 (2H, m), 7.61-7.72 (2H, m), 7.98 (1H, d, J = 2.0 Hz),
8.64-8.67 (1H, m), 9.37-9.41 (1H, m); 13C NMR (63 MHz,
CDCl3) δ 55.7, 99.4, 110.4, 115.6, 116.6, 117.0, 121.2, 124.8,
125.9, 128.5, 129.3, 133.8, 137.2, 140.9, 158.4; IR 1602 cm-1
HRMS calcd for C16H12N2O 248.0950, found 248.0962.
;
6-Methylpyrazolo[1,5-f ]phenanthridine (1o): 64%, yellowish
needles, mp 103-106 °C (MeOH); 1H NMR (250 MHz, CDCl3)
δ 2.52 (3H, s), 6.91 (1H, d, J = 2.0 Hz), 7.30-7.33 (1H, m),
7.41-7.48 (1H, m), 7.60-7.67 (1H, m), 7.85 (1H, d, J = 7.9 Hz),
8.00 (1H, d, J = 2.0 Hz), 8.04 (1H, s), 8.27-8.31 (1H, m), 8.58
(1H, dd, J = 1.2, 8.3 Hz); 13C NMR (63 MHz, CDCl3) δ 21.8,
98.6, 116.1, 121.0, 121.4, 122.6, 123.2, 124.1, 124.7, 126.5, 128.9,
129.2, 133.8, 137.3, 138.0, 140.8; IR 1619 cm-1; HRMS calcd for
C16H12N2 232.1000, found 232.1006.
6-Methoxypyrazolo[1,5-f ]phenanthridine (1p): 64%, white
needles, mp 124-126 °C (MeOH); 1H NMR (250 MHz, CDCl3)
δ 3.94 (3H, s), 6.82 (1H, d, J = 2.0 Hz), 7.09 (1H, dd, J 8.7, 2.4
Hz), 7.40-7.46 (1H, m), 7.59-7.65 (1H, m), 7.66 (1H, d, J = =
2.4 Hz), 7.88 (1H, d, J = 8.7 Hz), 7.94 (1H, d, J = 2.0 Hz),
8.21-8.24 (1H, m), 8.53-8.56 (1H, m); 13C NMR (63 MHz,
CDCl3) δ 55.4, 98.0, 105.5, 116.2, 116.3, 117.8, 120.9, 123.2,
Acknowledgment. This research was supported by the
University of the Basque Country/Basque Government
(Projects UNESCO07/08, GIU06/87/IT-349-07 and S-
PC08UN04) and the Spanish Ministry of Education and
Science (MEC CTQ2007-64501). S.H. thanks the University
of the Basque Country (UPV/EHU) for a predoctoral scho-
larship. The authors also thank Petronor, S.A. for generous
donation of hexane. Finally, technical and human support
provided by SGIker (UPV/EHU, MICINN, GV/EJ, ESF) is
gratefully acknowledged.
Supporting Information Available: Full experimental de-
tails, spectral data of all diarylpyrazoles and coupling products,
and copies of 1H and 13C NMR spectra. This material is
J. Org. Chem. Vol. 75, No. 2, 2010 441