Kumar et al.
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EtOAc/hexane). IR (cm-1) KBr: 3354, 1591, 1526, 1170, 752. 1H
NMR (400 MHz, CDCl3): δ 7.85 (d, J = 7.3 Hz, 2H), 7.66 (dd,
J = 7.4, 1.2 Hz, 2H), 7.53-7.47 (m, 3H), 7.38 (td, J = 7.1, 1.0 Hz,
1H), 7.24 (d, J = 7.7 Hz, 1H), 7.18 (dd, J = 8.3, 1.4 Hz, 1H), 6.99
(d, J = 7.1 Hz, 2H), 6.80 (td, J = 7.6, 1.7 Hz, 1H), 6.54 (s, 1H),
6.21 (br s, 1H), 3.87 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
159.1, 151.2, 140.7, 140.3, 137.9, 132.7, 129.4, 128.6, 127.9, 127.0,
125.3, 124.2, 121.6, 115.3, 114.0, 111.0, 94.9, 55.3. HRMS (ESI)
calcd for C22H19N3OBr [M þ Hþ] 420.0711, found 420.0711.
5(3)-(2-Bromoanilino)-3(5)-(4-methoxyphenyl)-1H-pyrazole
(5b). White solid (1.44 g, 84%); mp 123-124 °C; Rf 0.3 (1:4
EtOAc/hexane). IR (cm-1) KBr: 3392, 2931, 1595, 1525, 1450,
1251, 1021, 745. 1H NMR (500 MHz, CDCl3): δ 7.72 (br s, 1H),
7.51 (d, J = 6.9 Hz, 2H), 7.48 (dd, J = 8.3, 1.4 Hz, 1H), 7.45 (dd,
J = 8.6, 1.1 Hz, 1H), 7.15 (td, J = 7.9, 1.3 Hz, 1H), 6.84 (d, J =
6.9 Hz, 2H), 6.70 (td, J = 7.7, 1.5 Hz, 1H), 6.53 (brs, 1H), 6.22 (s,
1H), 3.77 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 160.0, 150.4,
145.0, 140.6, 132.6, 128.3, 126.9, 121.7, 120.9, 115.7, 114.3,
111.1, 92.6, 55.3. HRMS (ESI) calcd for C16H15N3OBr [M þ
Hþ] 344.0398, found 344.0398.
814. 1H NMR (400 MHz, CDCl3): δ 8.13 (br s, 1H), 7.68 (d, J=
7.8 Hz, 2H), 7.45 (t, J=7.9Hz, 2H), 7.23 (s, 1H), 7.21(t, J=7.4 Hz,
1H), 6.94 (s, 1H), 3.98 (s, 3H), 3.91 (s, 3H), 3.33 (sept, J=6.9 Hz,
1H), 1.52 (d, J=7.1 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ
151.9, 146.4, 145.0, 144.7, 139.3, 135.8, 129.5, 124.9, 118.2, 112.9,
109.2, 103.9, 96.8, 56.7, 56.2, 28.8, 22.2. HRMS (ESI) calcd for
C20H22N3O2 [M þ Hþ] 336.1712, found 336.1714.
General Procedure for Copper- catalyzed Synthesis of 4H-
pyrazolo[1,5-a]benzimidazoles (3). A mixture of pyrazole 5 (1.00
mmol), CuI (19 mg, 0.10 mmol), L-proline (23 mg, 0.20 mmol),
and NaH (0.10 g, 60%, 2.5 mmol) in dry DMF (10 mL) was
heated at 90 °C for 0.5-2.5 h under nitrogen atmosphere
(monitored by TLC). The reaction mixture was cooled to room
temperature and poured into water (50 mL). Extraction was
done with ethyl acetate (3 ꢀ 20 mL). The combined organic
extracts were washed with water (3ꢀ20 mL) and brine (1ꢀ30
mL) and dried over anhydrous Na2SO4. Solvent was evaporated
under reduced pressure, and the crude product was purified by
column chromatography over silica gel (100-200 mesh) using
hexane/ethyl acetate as eluent.
General Procedure for Palladium-Catalyzed Synthesis of
1-Arylpyrazolo[3,4-b]indoles (2). A mixture of 1-aryl pyrazole 1
(1.00 mmol), Pd(OAc)2 (22.4 mg, 0.10 mmol), n-Bu4NBr (0.32 g,
1.00 mmol), and K2CO3 (0.29 g, 2.50 mmol) in dry DMF
(10 mL) was heated at 140 °C for 2-30 h under nitrogen
atmosphere (monitored by TLC). Reaction mixture was cooled
to room temperature and poured into water (50 mL). Extraction
was done with ethyl acetate (3ꢀ20 mL). The combined organic
extracts were washed with water (3 ꢀ 20 mL) and brine (1 ꢀ 30
mL) and dried over anhydrous Na2SO4. Solvent was evaporated
under reduced pressure, and the crude product was purified by
column chromatography over silica gel (100-200 mesh) using
hexane/ethyl acetate as eluent.
3-(4-Methoxyphenyl)-1-phenylpyrazolo[3,4-b]indole (2b). White
solid (0.26 g, 76%); mp 213-214 °C; Rf 0.4 (1:4 EtOAc/hexane). IR
(cm-1) KBr: 3324, 2919, 1592, 1493, 1230, 836, 756. 1H NMR (400
MHz, CDCl3 þ a little DMSO-d6): δ 11.21 (br s, 1H), 7.81 (dd,
J=7.8, 2.0 Hz, 2H), 7.66 (d, J = 8.5 Hz, 2H), 7.63 (d, J=7.8 Hz,
1H), 7.28-7.22 (m, 3H), 6.97 (t, J = 7.8 Hz, 2H), 6.91 (t, J=7.4 Hz,
1H), 6.79 (dd, J = 8.8, 1.7 Hz, 2H), 3.60 (s, 3H). 13C NMR (100
MHz, CDCl3þlittle DMSO-d6): δ 158.9, 144.7, 143.3, 142.0, 138.4,
128.7, 127.5, 125.4, 124.4, 121.8, 119.4, 118.5, 117.7, 113.4, 111.8,
107.8, 54.5. HRMS (ESI) calcd for C22H18N3O[M þ Hþ] 340.1450,
found 340.1450.
1-(4-Fluorophenyl)-5-isopropyl-3-(4-trifluoromethylphenyl)
pyrazolo[3,4-b]indole (2h). White solid (0.27 g, 62%); mp 160-
161 °C; Rf 0.5 (1:4 EtOAc/hexane). IR (cm-1) KBr: 3453, 2959,
2924, 1568, 1511, 1324, 1105, 1065, 802. 1H NMR (400 MHz): δ
8.28 (d, J=8.0 Hz, 2H), 8.14 (s, 1H), 7.84 (d, J=8.1 Hz, 2H),
7.79-7.75 (m, 3H), 7.37 (d, J=8.3 Hz, 1H), 7.29-7.22 (m, 3H),
3.12 (sept, J= 6.8 Hz, 1H), 1.39 (d, J=6.8 Hz, 6H). 13C NMR (125
MHz, CDCl3): δ 160.8 (d, J=247.1 Hz), 145.7, 143.5, 142.4, 140.6,
137.1, 135.3, 130.0 (q, j=32.4 Hz), 127.3, 125.8 (d, J=3.6 Hz),
124.4 (q, J=272.3 Hz), 122.1, 120.9 (d, J = 8.4 Hz), 120.0, 117.6,
116.7 (d, J=24.0 Hz), 112.2, 109.8, 34.5, 24.8. HRMS (ESI) calcd
for C25H20N3F4 [M þ Hþ] 438.1593, found 438.1593.
2-(4-Methoxyphenyl)-4H-pyrazolo[1,5-a]benzimidazole (3b).
White solid (0.22 g, 84%); mp 204-205 °C; Rf 0.3 (1:3 EtOAc/
hexane). IR (cm-1) KBr: 3072, 2922, 1566, 1248, 1029, 835. 1H
NMR (400 MHz, CDCl3): δ 10.52 (s, 1H), 7.80-7.77 (m, 3H),
7.25 (d, J=7.8 Hz, 1H), 7.16-7.08 (m, 2H), 6.87 (d, J=7.8 Hz,
2H), 5.93 (s, 1H), 3.76 (s, 3H). 13C NMR (100 MHz, CDCl3 þ a
little DMSO-d6): δ 159.5, 155.8, 145.0, 135.3, 127.2, 126.9, 126.2,
122.9, 120.3, 113.9, 111.6, 110.1, 77.2, 55.2. HRMS (ESI) calcd
for C16H14N3O [M þ Hþ] 264.1137, found 264.1137.
2-(4-Trifluorophenyl)-7-isopropyl-4H-pyrazolo[1,5-a]benzimi-
dazoles (3f). White solid (0.26 g, 76%); mp 241-242 °C; Rf 0.3
(1:4 EtOAc/hexane). IR (cm-1) KBr: 3215, 3143, 2964, 602,
1385, 1323, 1160, 1124, 846. 1H NMR (400 MHz, CDCl3): δ 8.44
(br s, 1H), 8.06 (d, J=8.0 Hz, 2H), 7.81 (s, 1H), 7.70 (d, J= 8.0
Hz, 2H), 7.25 (d, J=8.3 Hz, 1H), 7.18 (d, J = 8.3 Hz, 1H), 6.13
(s, 1H), 3.07 (sept, J = 6.8 Hz, 1H), 1.33 (d, J=6.8 Hz, 6H). 13
C
NMR (100 MHz, CDCl3): δ 154.5, 144.8, 142.9, 137.7, 133.1,
129.7 (d, j=33 Hz), 126.5, 126.0, 125.6, 122.6, 111.3, 108.2, 78.6,
34.2, 24.3. HRMS (ESI) calcd for C19H17N3F3 [M þ Hþ]
344.1375, found 344.1375.
2-(Furan-2-yl)-4H-pyrazolo[1,5-a]benzimidazole (3h). White
solid (0.21 g, 94%); mp 234-235 °C; Rf 0.3 (1:3 EtOAc/hexane).
1
IR (cm-1) KBr: 3424, 2924, 1598, 1482, 1309, 1010, 740. H
NMR (400 MHz, DMSO-d6): δ 11.56 (s, 1H), 7.77 (d, J=7.8 Hz,
1H), 7.72 (d, J=1.7 Hz, 1H), 7.44 (d, J=8.0 Hz, 1H), 7.28 (t,
J=7.7 Hz, 1H), 7.19 (t, J=7.5 Hz, 1H), 6.83 (d, J=3.2 Hz, 1H),
6.58 (dd, J=3.3 Hz, 1.7 Hz, 1H), 6.13 (s, 1H). 13C NMR (100
MHz, DMSO-d6): δ 149.3, 147.3, 144.5, 142.4, 135.4, 125.3,
123.4, 120.3, 111.9, 111.6, 109.7, 106.1, 77.1. HRMS (ESI) calcd
for C13H10N3O [M þ Hþ] 224.0824, found 224.0825.
2-Isopropyl-6,7-dimethoxy-4H-pyrazolo[1,5-a]benzimidazoles
(3k). Red solid (0.21 g, 81%); mp 63-64 °C; Rf 0.3 (1:1 EtOAc/
hexane). IR (cm-1) KBr: 3330, 2927, 1590, 1500, 1273, 1152,
794. 1H NMR (400 MHz, CDCl3): 9.45 (s, 1H), 7.24 (s, 1H), 6.78
(s, 1H), 5.56 (s, 1H), 3.74 (s, 3H), 3.69 (s, 3H), 3.07 (sept, J=6.9
Hz, 1H), 1.29 (d, J=7.1 Hz, 6H). 13C NMR (100 MHz, CDCl3):
δ 164.0, 146.4, 144.9, 144.2, 128.1, 119.8, 96.6, 94.8, 78.0, 56.5,
56.4, 29.0, 23.1. HRMS (ESI) calcd for C14H18N3O2 [M þ Hþ]
260.1399, found 260.1397.
3-(Furan-2-yl)-1-phenylpyrazolo[3,4-b]indole (2j). Pale yellow
solid (0.20 g, 68%); mp 221-222 °C; Rf 0.4 (1:4 EtOAc/hexane). IR
(cm-1) KBr: 3069, 2955, 1561, 1514, 1414, 1230, 742. 1HNMR(400
MHz, CDCl3þlittle DMSO-d6): δ 11.07 (br s, 1H), 7.90 (t, J=6.5
Hz, 1H), 7.78-7.76 (m, 2H), 7.52-7.50 (m, 1H), 7.37-7.30 (m,
3H), 7.12-7.05 (m, 3H), 6.92 (dd, J=6.6, 3.4 Hz, 1H), 6.47-6.44
(m, 1H). 13C NMR (100 MHz, CDCl3þlittle DMSO-d6): δ 148.2,
144.7, 142.4, 142.1, 138.6, 135.4, 129.0, 125.1, 122.5, 120.0. HRMS
(ESI) calcd for C19H14N3O [M þ Hþ] 300.1137, found 300.1143.
5,6-Dimethoxy-3-isopropyl-1-phenylpyrazolo[3,4-b]indole (2m).
White solid (0.17 g, 52%); mp 203-204 °C; Rf 0.2 (1:3 EtOAc/
hexane). IR (cm-1) KBr: 3197, 2959, 2930, 1596, 1499, 1196, 1141,
Acknowledgment. S.K. thanks CSIR, New Delhi, for a
fellowship.
Supporting Information Available: Experimental details and
spectroscopic data for all new compounds. ORTEP diagram of
2b. This material is available free of charge via the Internet at
J. Org. Chem. Vol. 74, No. 18, 2009 7051