9278
S. Chimichi et al. / Tetrahedron 64 (2008) 9275–9279
chromatography, respectively. Solvents were removed under re-
duced pressure. All 1D and 2D NMR experiments were performed
4.2.4. 3,5-Dimethyl-2-phenyl-2,5-dihydro-4H-pyrazolo[4,3-c]-
quinolin-4-one (4b)
on
100.57 MHz for 13C), with a 5 mm indirect detection probe equip-
ped with a gradient coil, at 298 K. Chemical shifts ( in ppm) were
a
Varian Mercuryplus spectrometer (399.95 MHz for 1H,
Yellowish solid; mp 181–183 ꢀC; Rf (ethyl acetate/petroleum
ether 40/70¼1:2) 0.31; IR (KBr) 1651, 1595, 1493, 1345, 1258 cmꢁ1
;
d
1H NMR (400 MHz, CDCl3)
d 2.78 (3H, s, CH3), 3.72 (3H, s, N–CH3),
referenced to the solvent CDCl3, 7.26 for 1H and 77.00 for 13C. All
coupling constants are in hertz. Assignments are made using 1H,
13C, DEPT and NOESY-1D experiments and gHSQC, gHMBC, gHMQC
and gCOSY 2D experiments. All pulse sequences were used as
provided by Varian and processing was done using standard Varian
methods.
7.25–7.29 (1H, m, H-8), 7.37–7.39 (1H, m, H-6), 7.50–7.57 (6H, m,
H-7 and Ar–H), 8.32 (1H, dd, 3J¼8.2 Hz, 4J¼1.8 Hz, H-9); 13C NMR
(100.57 MHz, CDCl3)
d 160.4 (s, C-4), 147.8 (s, C-9b), 142.2 (s, C-3),
139.5 (s, C-5a), 138.7 (s, C-10), 129.7 (d, C-7), 129.4 (d, Ar), 129.0 (d,
Ar), 125.8 (d, Ar), 123.3 (d, C-9), 122.4 (d, C-8), 115.7 (s, C-9a), 113.1
(d, C-6), 110.6 (s, C-3a), 28.7 (q, 5N–CH3), 12.0 (q, 3-CH3); EIMS m/z
(%): 289 (Mþ, 100), 273 (11), 145 (18), 77 (35), 51 (25). Anal. Calcd
for C18H15N3O: C, 74.72; H, 5.23; N, 14.52. Found: C, 74.46; H, 5.37;
N, 14.75.
4.2. General procedure for the preparation of compounds 3
and 4
To a stirred solution of 3-acetyl-4-methoxy-1-methylquinolin-
2(1H)-one (2) (162 mg, 0.70 mmol) in EtOH (8 mL) hydrazine or
hydrazine hydrochloride (0.80 mmol) was added and the reaction
mixture heated at reflux for 3 h. After cooling, removal of the sol-
vent left a solid, which was crystallized or separated by column
chromatography with the appropriate eluant.
4.3. 1,2-Dihydro-3-(phenylcarbonyl)-1-methyl-2-
oxoquinolin-4-yl-4-methylbenzensulfonate (6)
A solution of 9 (250 mg, 0.895 mmol), tosyl chloride (190 mg,
1.00 mmol) and triethylamine (140 mL, 1.00 mmol) in dry toluene
(6 mL) was heated under reflux for 5 h. After cooling to rt
dichloromethane was added and the organic phase was washed
several times with diluted hydrochloric acid (3ꢂ10 mL) in a sepa-
ratory funnel. The organic phase was dried with sodium sulfate and
the solvent removed under reduced pressure to give a yellow solid
(0.309 g, 79%) that was crystallized from EtOH. Yellowish needles;
mp 201 ꢀC, dec (lit.10 199 ꢀC, dec from toluene).
4.2.1. 1,3,5-Trimethyl-1,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one (3a)
White solid; mp 250 ꢀC, dec (from EtOH); IR (KBr) 2936, 1651,
1577, 1497, 1433, 1328 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 2.66 (3H,
s, CH3), 3.69 (3H, s, 5N–CH3), 4.30 (3H, s, 1N–CH3), 7.30 (1H, ddd,
3J¼8.0, 7.8 Hz, 4J¼1.0 Hz, H-8), 7.43 (1H, dd, 3J¼8.4 Hz, 4J¼1.0 Hz,
H-6), 7.56 (1H, ddd, 3J¼8.6, 7.8 Hz, 4J¼1.4 Hz, H-7), 8.04 (1H, dd,
3J¼8.0 Hz, 4J¼1.4 Hz, H-9); 13C NMR (100.57 MHz, CDCl3)
d 159.3 (s,
4.4. 1,5-Dimethyl-3-phenyl-1,5-dihydro-4H-pyrazolo[4,3-c]-
quinolin-4-one (7a)
C-4), 147.4 (s, C-3), 139.8 (s, C-5a), 139.7 (s, C-9b), 127.9 (d, C-7),
122.8 (d, C-9), 122.0 (d, C-8), 115.8 (d, C-6), 112.5 (s, C-9a), 110.9 (s,
3a), 39.9 (q, 1N–CH3), 28.9 (q, 5N–CH3), 12.8 (q, 3-CH3); EIMS m/z
(%): 227 (Mþ, 100), 212 (14), 184 (12), 113 (18), 77 (10). Anal. Calcd
for C13H13N3O: C, 68.70; H, 5.77; N, 18.49. Found: C, 68.86; H,
5.66; 18.73.
This compound was obtained from compound
6 (51 mg,
0.12 mmol) with methylhydrazine (14.8 L, 0.28 mmol) in EtOH
m
(5 mL) for 4 h at rt as described below for 8b (method B). Yellowish
solid; mp 146–147 ꢀC (from EtOH); IR (CDCl3) 3010, 1653, 1578,
1104 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 3.76 (3H, s, 5N–CH3), 4.45
(3H, s, 1N–CH3), 7.35 (1H, ddd, 3J¼8.3, 7.2 Hz, 4J¼1.2 Hz, H-8), 7.38–
7.50 (4H, m, H-6, H-30, H-40), 7.62 (1H, ddd, 3J¼8.6, 7.2 Hz, 4J¼1.4 Hz,
H-7), 8.09–8.12 (2H, m, H-20), 8.16 (1H, dd, 3J¼8.3 Hz, 4J¼1.4 Hz,
4.2.2. 3,5-Dimethyl-1-phenyl-1,5-dihydro-4H-pyrazolo[4,3-c]-
quinolin-4-one (3b)
White solid; mp 184–185 ꢀC (from EtOH) (lit.6d 190–193 ꢀC from
ligroin); IR (KBr) 1655, 1570, 1345, 1255 cmꢁ1 1H NMR (400 MHz,
;
H-9); 13C NMR (100.57 MHz, CDCl3)
d 158.7 (s, C-4), 149.9 (s, C-3),
CDCl3)
d
2.77 (3H, s, CH3), 3.76 (3H, s, N–CH3), 6.98 (1H, ddd, 3J¼8.2,
140.6 (s, C-9b), 139.5 (s, C-5a), 131.9 (s, C-10), 129.8 (d, C-7), 129.4 (d,
Ar), 128.5 (d, Ar), 128.0 (d, Ar), 122.8 (d, C-9), 121.9 (d, C-8), 115.8 (d,
C-6), 112.5 (s, C-9a), 109.9 (s, C-3a), 40.7 (q, 1N–CH3), 29.4 (q, 5N–
CH3); EIMS m/z (%): 289 (Mþ, 100), 274 (29), 144 (27), 137 (22), 77
(18), 63 (6), 51 (15). Anal. Calcd for C18H15N3O: C, 74.72; H, 5.23; N,
14.52. Found: C, 74.88; H, 5.04; N, 14.61.
7.1 Hz, 4J¼1.2 Hz, H-8), 7.26 (1H, dd, 3J¼8.2 Hz, 4J¼1.4 Hz, H-9), 7.42
(1H, dd, 3J¼8.6 Hz, 3J¼1.2 Hz, H-6), 7.49 (1H, ddd, 3J¼8.6, 7.1 Hz,
4J¼1.4 Hz, H-7), 7.53–7.60 (5H, m, Ar–H); 13C NMR (100.57 MHz,
CDCl3)
d 159.5 (s, C-4), 149.3 (s, C-3), 139.8 (s, C-5a), 140.4 (s, C-9b/
C-10), 140.3 (s, C-10/C-9b), 130.0 (d, C-7), 129.8 (d, Ar), 129.7 (d, Ar),
127.1 (d, Ar), 123.1 (d, C-9), 121.6 (d, C-8), 115.6 (d, C-6), 112.1 (s,
C-9a), 111.3 (s, 3a), 29.0 (q, 5N–CH3), 13.2 (q, 3-CH3). Anal. Calcd
for C18H15N3O: C, 74.72; H, 5.23; N, 14.52. Found: C, 74.53; H, 5.29;
N, 14.66.
4.5. 5-Methyl-1,3-diphenyl-1,5-dihydro-4H-pyrazolo[4,3-c]-
quinolin-4-one (7b)
4.2.3. 2,3,5-Trimethyl-2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-
one (4a)
This compound was obtained from compound 5 (52 mg,
0.18 mmol) with phenylhydrazine hydrochloride (30 mg, 0.21 mmol)
in ethylene glycol for 1 h as described below for 8b (method A).
White solid; mp 195–196 ꢀC (from EtOH) (lit.6a 200–202 ꢀC from
ligroin); IR (KBr) 1651, 1615, 1596 cmꢁ1; 1H NMR (400 MHz, CDCl3)
White solid; mp 152–154 ꢀC (from EtOH); IR (KBr) 2927, 1656,
1592, 1426, 1342, 1254 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 2.75 (3H,
s, CH3), 3.66 (3H, s, 5N–CH3), 4.00 (3H, s, 2N–CH3), 7.25 (1H, ddd,
3J¼7.8, 7.2 Hz, 4J¼1.0 Hz, H-8), 7.33 (1H, dd, 3J¼8.6 Hz, 4J¼1.0 Hz,
H-6), 7.49 (1H, ddd, 3J¼8.6, 7.2 Hz, 4J¼1.6 Hz, H-7), 8.20 (1H, dd,
d
3.78 (3H, s, N–CH3), 6.99 (1H, ddd, 3J¼8.1, 7.0 Hz, 4J¼1.2 Hz, H-8),
7.26 (1H, dd, 3J¼8.1 Hz, 4J¼1.4 Hz, H-9), 7.41–7.53 (5H, m, H-6, H-7,
3J¼7.8 Hz, 4J¼1.6 Hz, H-9); 13C NMR (100.57 MHz, CDCl3)
d
160.0 (s,
H-30, H-40), 7.61–7.62 (5H, m, Ar–H), 8.15–8.19 (2H, m, H-20); 13C
C-4), 141.1 (s, C-3), 139.0 (s, C-5a), 144.7 (s, C-9b), 129.0 (d, C-7),
122.5 (d, C-9), 122.0 (d, C-8), 115.7 (s, C-9a), 114.9 (d, C-6), 109.4 (s,
C-3a), 36.4 (q, 2N–CH3), 28.4 (q, 5N–CH3), 10.5 (q, 3-CH3); EIMS m/z
(%): 227 (Mþ, 100), 212 (15), 196 (11), 113 (14), 77 (9), 56 (35), 51
(10). Anal. Calcd for C13H13N3O: C, 68.70; H, 5.77; N,18.49. Found: C,
68.84; H, 5.97; N, 18.32.
NMR (100.57 MHz, CDCl3) d 158.8 (s, C-4), 151.5 (s, C-3), 141.3 (s,
C-9b), 140.5 (s, C-100), 139.6 (s, C-5a), 131.7 (s, C-10), 130.1 (d, C-7),
129.9 (d, Ar), 129.7 (d, C-20), 128.7 (d, C-40), 128.0 (d, C-30), 127.3 (d,
Ar), 123.2 (d, C-9), 121.5 (d, C-8), 115.5 (d, C-6), 111.9 (s, C-9a), 110.1
(s, C-3a), 29.4 (q, 5N–CH3). Anal. Calcd for C23H17N3O: C, 78.61; H,
4.88; N, 11.96. Found: C, 78.52; H, 4.98; N, 12.04.