Chebanov et al.
single mode microwave reactor at 150 °C for 15 min with magnetic
stirring. After cooling to ambient conditions by compressed air, 4
mL of a EtOH-H2O mixture (1:1) was added to the crude reaction
mixture and heated to 50-60 °C with vigorous stirring. After
cooling the precipitate was removed by filtration, washed with
EtOH-H2O (1:1), and dried at room temperature to produce the
desired pyrazoloquinolinone 4a-g in >98% purity (1H NMR and
HPLC).
7.92-8.00 (m, 2H), 10.13 (s, 1H), 12.70 (s, 1H); 13C NMR (DMSO-
d6, 90 MHz) δ 27.0, 29.3, 32.4, 36.2, 41.3, 50.7, 102.5, 106.9, 123.4,
126.5, 128.5, 129.2, 129.2, 129.6, 138.4, 145.8, 148.2, 153.3, 155.3,
193.2; MS (EI, 70 eV) m/z 414 (M, 34), 415 (M+, 12), 292 (100),
293 (17). Anal. Calcd for C24H22N4O3: C, 69.55; H, 5.35; N, 13.52.
Found: C, 69.29; H, 5.18; N, 13.58.
7,7-Dimethyl-3-phenyl-4-[2-(trifluoromethyl)phenyl]-1,4,6,7,8,9-
hexahydro-1H-pyrazolo[3,4-b]quinolin-5-one (4f). Yield 86%, mp
247-250 °C; 1H NMR (DMSO-d6, 360 MHz) δ 0.86 (s, 3H), 0.99
(s, 3H), 1.89 (d, 1H, J ) 15.9 Hz), 2.11 (d, 1H, J ) 15.9 Hz), 2.39
(d, 1H, J ) 16.6 Hz), 2.52 (d, 1H, J ) 16.6 Hz), 5.69 (s, 1H),
7.04-7.13 (m, 2H), 7.15-7.22 (m, 1H), 7.23-7.31 (m, 4H),
7.33-7.36 (m, 1H), 7.36-7.45 (m, 1H), 9.99 (s, 1H), 12.43 (br s,
1H); 13C NMR (DMSO-d6, 90 MHz) δ 27.1, 29.3, 32.4, 41.5, 50.9,
103.8, 108.2, 126.3, 126.6, 127.9, 128.6, 130.0, 131.6, 132.0, 139.6,
147.6, 147.7, 152.8, 193.0; MS (EI, 70 eV) m/z 437 (M, 22), 438
(M+, 8), 292 (100), 293 (18). Anal. Calcd for C25H22F3N3O: C,
68.64; H, 5.07; N, 9.61. Found: C, 68.45; H, 4.98; N, 9.72.
4-(4-Methylphenyl)-3-phenyl-1,4,6,7,8,9-hexahydro-1H-pyra-
zolo[3,4-b]quinolin-5-one (4g). Yield 70%, mp >310 °C; 1H NMR
(DMSO-d6, 360 MHz) δ 1.61-1.78 (m, 1H), 1.78-1.82 (m, 1H),
2.12 (s, 3H), 2.14-2.27 (m, 2H), 2.50-2.60 (m, 2H), 5.35 (s, 1H),
6.83-6.93 (m, 2H), 6.89 (d, 2H, J ) 8.0 Hz), 7.00 (d, 2H, J ) 8.0
Hz), 7.23-7.31 (m, 1H), 7.33-7.42 (m, 2H), 7.47-7.57 (m, 2H),
9.93 (s, 1H), 12.56 (s, 1H); 13C NMR (DMSO-d6, 90 MHz) δ 21.0,
21.4, 28.1, 35.0, 37.4, 103.8, 109.8, 126.3, 127.8, 128.3, 129.2,
130.0, 134.7, 137.6, 145.3, 148.6, 154.4, 193.6; MS (EI, 70 eV),
m/z 355 (M, 37), 356 (M+, 10), 264 (M, 100). Anal. Calcd for
C23H21N3O: C, 77.72; H, 5.96; N, 11.82. Found: C, 77.95; H, 5.98;
N, 11.60.
4-(4-Fluorophenyl)-3-phenyl-1,4,6,7,8,9-hexahydro-1H-pyra-
zolo[3,4-b]quinolin-5-one (4h). Yield 85%, mp >300 °C; 1H NMR
(DMSO-d6, 360 MHz) δ 1.73-1.89 (m, 2H), 2.14-2.18 (m, 2H),
2.53-2.56 (m, 2H), 5.36 (s, 1H), 6.75-6.95 (m, 2H), 6.97-7.18
(m, 2H), 7.19-7.40 (m, 3H), 7.40-7.55 (m, 2H), 9.96 (s, 1H),
12.59 (s, 1H); 13C NMR (DMSO-d6, 90 MHz) δ 21.4, 28.1, 34.9,
37.4, 56,5, 103.5, 109.4, 114.7, 114.9, 126.4, 128.4, 129.2, 129.6,
129.7, 129.9, 137.8, 144.4, 144.4, 148.5, 154.6, 159.6, 161.5, 193.7;
MS (EI, 70 eV), m/z 359 (M, 39), 360 (M+, 9), 264 (100). Anal.
Calcd for C22H18FN3O: C, 73.52; H, 5.05; N, 11.69. Found: C,
73.33; H, 4.95; N, 11.77.
7,7-Dimethyl-3,4-diphenyl-1,4,6,7,8,9-hexahydro-1H-pyrazo-
lo[3,4-b]quinolin-5-ones (4a). Yield 85%, mp >300 °C; 1H NMR
(DMSO-d6, 360 MHz) δ 0.82 (s, 3H), 0.98 (s, 3H), 1.92 (d, 1H, J
) 16.3 Hz), 2.14 (d, 1H, J ) 16.3 Hz), 2.33 (d, 1H, J ) 16.3 Hz),
2.45 (d, 1H, J ) 16.3 Hz), 5.31 (s, 1H), 6.86-7.17 (m, 5H),
7.19-7.43 (m, 3H), 7.45-7.57 (m, 2H), 9.91 (br s, 1H), 12.55 (br
s, 1H); 13C NMR (DMSO-d6, 90 MHz) δ 27.0, 29.45, 32.42, 35.67,
41.37, 50.9, 56.55, 103.8, 108.3, 125.8, 126.4, 127.9, 128.1, 128.3,
129.2, 130.0, 137.8, 148.04, 148.6, 152.6, 193.2; MS (EI, 70 eV)
m/z 369 (M, 19), 292 (93), 293 (18). Anal. Calcd for C24H23N3O:
C, 78.02; H, 6.27; N, 11.37. Found: C, 77.92; H, 6.25; N, 11.41.
7,7-Dimethyl-4-(4-methylphenyl)-3-phenyl-1,4,6,7,8,9-hexahy-
dro-1H-pyrazolo[3,4-b]quinolin-5-one (4b). Yield 86%, mp
207-209 °C; 1H NMR (DMSO-d6, 360 MHz) δ 0.84 (s, 3H), 0.99
(s, 3H), 1.95 (d, 1H, J ) 16.9 Hz), 2.12 (s, 3H), 2.15 (d, 1H, J )
16.9 Hz), 2.35 (d, 1H, J ) 16.9 Hz), 2.48 (d, 1H, J ) 16.9 Hz),
5.31 (s, 1H), 6.89 (d, 2H, J ) 8.0 Hz), 7.01 (d, 2H, J ) 8.0 Hz),
7.22-7.31 (m, 1H), 7.32-7.42 (m, 2H), 7.49-7.58 (m, 2H), 9.91
(s, 1H), 12.56 (br s, 1H); 13C NMR (DMSO-d6, 90 MHz) δ 20.8,
26.2, 28.7, 31.6, 34.0, 40.6, 50.1, 103.2, 107.8, 110.5, 125.6, 127.5,
128.1, 128.4, 139.5, 151.6, 156.6, 192.5; MS (EI, 70 eV) m/z 383
(M, 60), 384 (M+, 25), 292 (100), 293 (20). Anal. Calcd for
C25H25N3O: C, 78.30; H, 6.57; N, 10.96. Found: C, 78.15; H, 6.54;
N, 11.11.
7,7-Dimethyl-4-(4-methoxyphenyl)-3-phenyl-1,4,6,7,8,9-hexahy-
dro-1H-pyrazolo[3,4-b]quinolin-5-one (4c). Yield 76%, mp
183-186 °C; 1H NMR (DMSO-d6, 360 MHz) δ 0.83 (s, 3H), 0.99
(s, 3H), 1.95 (d, 1H, J ) 16.3 Hz), 2.14 (d, 1H, J ) 16.3 Hz), 2.35
(d, 1H, J ) 16.3 Hz), 2.47 (d, 1H, J ) 16.3 Hz), 3.60 (s, 3H), 5.28
(s, 1H), 6.65 (d, 2H, J ) 8.6 Hz), 7.00 (d, 2H, J ) 8.6 Hz),
7.23-7.33 (m, 1H), 7.33-7.42 (m, 2H), 7.46-7.59 (m, 2H), 9.89
(s, 1H), 12.56 (br s, 1H); 13C NMR (DMSO-d6, 90 MHz) δ 27.0,
29.4, 32.48 34.7, 41.3, 50.9, 55.2, 104.0, 108.6, 113.4, 126.3, 128.3,
128.8, 129.2, 130.1, 137.6, 140.3, 148.6, 152.4, 157.4, 193.3; MS
(EI, 70 eV) m/z 399 (M, 58), 400 (M+, 15), 292 (100), 293 (19).
9-Aryl-2-phenyl-5,6,7,9-tetrahydropyrazolo[5,1-b]quinazolin-
8(4H)-ones (5a-h).
´
General Procedure (Table 2). A mixture of 5-amino-3-
phenylpyrazole 1 (1.30 mmol, 1 equiv), cyclic 1,3-diketone 2a,b
(1.30 mmol, 1 equiv), the appropriate aromatic aldehyde 3a-e,h
(1.3 mmol, 1 equiv), and 2 mL of ethanol was sonicated in a
standard ultrasonic bath (44.2 kHz) at room temperature for 30 min
in a 5 mL round-bottom flask equipped with condenser. The
precipitates formed were removed by filtration, washed with EtOH-
H2O (1:1) and dried at room temperature to produce the desired
pyrazoloquinazolinones 5a-h. The work up procedure for pyra-
zoloquinazolinones 5g,h involved evaporation under reduced pres-
sure and crystallization of the resulting crude oil with acetonitrile
at room temperature. The purity of pyrazoloquinazolinones 5a-h
was >98% (1H NMR and HPLC).
Anal. Calcd for C25H25N3O2: C, 75.16; I, 6.31; N, 10.52. Found:
C, 75.01; I, 6.28; N, 10.41.
´
4-(4-Bromophenyl)-7,7-dimethyl-3-phenyl-1,4,6,7,8,9-hexahy-
dro-1H-pyrazolo[3,4-b]quinolin-5-one (4d). Yield 91%, mp
195-197 °C; 1H NMR (DMSO-d6, 360 MHz) δ 0.83 (s, 3H), 0.99
(s, 3H), 1.96 (d, 1H, J ) 16.3 Hz), 2.16 (d, 1H, J ) 16.3 Hz), 2.36
(d, 1H, J ) 16.5 Hz), 2.48 (d, 1H, J ) 16.5 Hz), 5.33 (s, 1H), 7.06
(d, 2H, J ) 8.6 Hz), 7.23-7.33 (m, 3H), 7.33-7.43 (m, 2H),
7.47-7.55 (m, 2H), 10.00 (s, 1H), 12.63 (s, 1H); 13C NMR (DMSO-
d6, 90 MHz) δ 27.0, 29.4, 32.4, 35.4, 41.3, 50.8, 103.2, 107.7, 118.8,
126.4, 128.4, 129.2, 129.8, 130.2, 130.9, 138.0, 147.3, 148.4, 152.8,
193.2; MS (EI, 70 eV) m/z 447 (M-, 21), 448 (M, 8), 449 (M+,
24), 292 (100), 293 (19). Anal. Calcd for C24H22BrN3O: C, 64.29;
H, 4.95; Br, 17.82; N, 9.37. Found: C, 64.10; H, 4.88; Br, 17.65;
N, 9.21.
2,9-Diphenyl-6,6-dimethyl-5,6,7,9-tetrahydropyrazolo[5,1-
1
b]quinazolin-8(4H)-one (5a). Yield 67%, mp 202-204 °C; H
NMR (DMSO-d6, 200 MHz) δ 0.91 (s, 3H), 1.03 (s, 3H), 2.07 (d,
1H, J ) 16.2 Hz), 2.17 (d, 1H, J ) 16.2 Hz), 2.44 (d, 1H, J )
17.2 Hz), 2.58 (d, 1H, J ) 17.2 Hz), 6.17 (s, 2H), 7.09-7.40 (m,
8H), 7.62-7.75 (m, 2H), 10.52 (s, 1H); 13C NMR (DMSO-d6, 125
MHz) δ 27.2, 29.2, 32.6, 50.4, 58.0, 85.9, 105.4, 125.5, 127.1,
127.7, 128.2, 128.6, 128.9, 133.6, 138.8, 143.4, 149.7, 150.7, 192.8;
MS (EI, 70 eV) m/z 369 (M, 100), 368 (M-, 32), 292 (99), 159
(37). Anal. Calcd for C24H23N3O: C, 78.02; H, 6.27; N, 11.37.
Found: C, 78.13; H, 6.48; N, 11.07.
7,7-Dimethyl-4-(4-nitrophenyl)-3-phenyl-1,4,6,7,8,9-hexahy-
dro-1H-pyrazolo[3,4-b]quinolin-5-one (4e). Yield 83%, mp
196-198 °C; 1H NMR (DMSO-d6, 360 MHz) δ 0.83 (s, 3H), 0.99
(s, 3H), 1.96 (d, 1H, J ) 15.9 Hz), 2.16 (d, 1H, J ) 15.9 Hz), 2.39
(d, 1H, J ) 16.3 Hz), 2.55 (d, 1H, J ) 16.3 Hz), 5.50 (s, 1H),
7.23-7.31 (m, 1H), 7.32-7.42 (m, 4H), 7.44-7.54 (m, 2H),
(19) (a) Moon, B.; Han, S.; Yoon, Y.; Kwon, H. Org. Lett. 2005, 7, 1031.
(b) Miyano, S.; Abe, N.; Sumoto, K.; Teramoto, K. J. Chem. Soc., Perkin Trans.1
1976, 1, 1146. (c) Chern, J.-W.; Chen, H.-T.; Lai, N.-Y.; Wu, K.-R.; Chern,
Y.-C. Chem. Pharm. Bull. 1998, 46, 928.
6,6-Dimethyl-9-(4-methylphenyl)-2-phenyl-4,5,6,7,8,9-hexahy-
dropyrazolo[5,1-b]quinazolin-8-one (5b). Yield 56%, mp 228-230
5116 J. Org. Chem. Vol. 73, No. 13, 2008