Autor/ name of journal 00 (0000) pppp-pppp
PQ 3 (yellow solid, 2.5 g, 90%) was obtained from 13a (2.4 g, 7.62 mmol) according to general procedure D; m.p.
1
decomposition >300 °C; H NMR (400 MHz, DMSO-d6) δ 3.78 (s, 3H, OCH3), 7.01 (d, J = 9.2 Hz, 2H, H3’ and H5’), 7.69
(dd, J = 10.1, 2.0 Hz, 1H, H8), 7.88 (d, J = 1.9 Hz, 1H), 8.06 (d, J = 9.2 Hz, 2H), 8.13 (d, J = 8.6 Hz, 1H), 8.74 (s, 1H), 12.80
(br s, 1H); 13C NMR (101 MHz, DMSO-d6) δ 55.3, 106.7, 113.9, 117.8, 120.4, 121.8, 122.5, 124.1, 129.2, 133.4, 136.5, 139.6,
141.9, 156.0, 160.9.
5.1.5.2
7-Fluoro-2-(4-methoxyphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (4)
PQ 4 (yellow solid, 164 mg, 90%) was obtained from 13b (150 mg, 0.59 mmol) according to general procedure D; m.p.
decomposition >300 °C; 1H NMR (400 MHz, DMSO-d6) δ 3.78 (s, 3H), 7.01 (d, J = 9.2 Hz, 2H), 7.69 (dd, J = 10.1, 2.0 Hz,
1H), 7.88 (d, J = 1.9 Hz, 1H), 8.06 (d, J = 9.2 Hz, 2H), 8.13 (d, J = 8.6 Hz, 1H), 8.74 (s, 1H), 12.80 (br s, 1H); 13C NMR (101
MHz, DMSO-d6) δ 55.2, 105.8 (d, 2JC,F = 25.1 Hz), 106.8, 113.8, 114.7 (d, J2C,F=27 Hz), 115.5, 120.4, 124.7 (d, 3JC,F = 10 Hz),
133.4, 136.7 (d, J1C,F = 11.8 Hz), 139.6, 142.1, 155.9, 160.9, 163.5 (d, 1JC,F =246.9 Hz); HR-MS: m/z 305.0824 [M+H]+ (calc.
305.0833, diff. -2.94 ppm).
5.1.5.2
7-Chloro-2-(4-methoxyphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (5)
PQ 5 (yellow solid, 110 mg, 92%) was obtained from 13c (100 mg, 0.37 mmol) according to general procedure D; m.p.
decomposition >330 °C; 1H-NMR (400 MHz, DMSO-d6): δ 3.78 (s, 3H), 7.02 (d, J = 9.2 Hz, 2H), 7.58 (dd, J = 8.6, 2.1 Hz,
1H), 7.73 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 9.2 Hz, 2H), 8.20 (d, J = 8.6 Hz, 1H), 8.77 (s, 1H), 12.78 (s, 1H); 13C-NMR (101
MHz, DMSO-d6) δ 55.3 , 106.8 , 113.9 , 117.5 , 118.8 , 120.4 , 124.0 , 126.5 , 133.4 , 134.1 , 136.4 , 139.8 , 141.9 , 156.0 ,
160.9; HR-MS: m/z 326.0708 [M+H]+ (calc. 326.0696, diff. -5.64 ppm).
5.1.5.3
7-Trifluoromethyl-2-(4-methoxyphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (6)
PQ 7 (yellow solid, 80 mg, 68%) was obtained from 13c (100 mg, 0.37 mmol) according to general procedure D; m.p.
1
decomposition >330 °C; H NMR (400 MHz, DMSO-d6) δ 3.79 (s, 3H), 7.02 (d, J = 9.2 Hz, 2H), 7.81 (dd, J = 8.4, 1.6 Hz,
1H), 8.02 (d, J = 1.7 Hz, 1H), 8.09 (d, J = 9.2 Hz, 1H), 8.39 (d, J = 8.4 Hz, 1H), 8.83 (s, 1H). 13C NMR (151 MHz, DMSO-d6)
δ 55.7, 107.3, 114.3, 117.9 (q, 3JC,F=3.9 Hz), 121.0, 122.3, 122.5 (q, 3JC,F =3.2 Hz), 124.0, 124.2 (q, 1JC,F =272.2 Hz), 129.8 (q,
2JC,F =32.5 Hz), 133.9, 136.7, 141.5, 142.2, 156.5, 161.4; HR-MS: m/z 360.0975 [M+H]+ (calc. 360.0954, diff. -4.8 ppm).
5.1.5.4
7-Methyl-2-(4-methoxyphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (7)
In a vial equipped with a magnetic stirrer and screw cap, PQ 3 (40 mg; 0.1 mmol, 1 equiv.) was suspended in dioxane (1.5
mL). Tetrakis(triphenylphosphine)palladium (0) (0.2 equiv.), K2CO3 (2.5 equiv.) and trimethylboroxine (3 equiv.) were added
under argon and the reaction mixture was refluxed overnight for 24 h. The reaction mixture was filtered hot trough silica and
washed with warm MeOH. The product (yellow solid, 30 mg, 90%) was purified via HPLC; m.p. decomposition >315 °C; 1H-
NMR (DMSO-d6, 400MHz): δ 2.46 (s, 3H), 3.78 (s, 3H), 7.01 (d, J = 9.2 Hz, 2H), 7.37 (dd, J = 8.3, 1.5 Hz, 1H), 7.49 (s, 1H),
8.09 (dd, J = 8.6, 3.2 Hz, 3H), 8.65 (s, 1H); 13C NMR (DMSO-d6, 50MHz): δ 21.8, 55.7, 106.6, 114.2, 116.9, 119.8, 120.7,
122.4, 128.2, 134.1,136.4, 139.7, 140.4, 143.2, 156.2, 161; HR-MS: m/z 306.1254 [M+H]+ (calc. 305.1164, diff. -5.24 ppm).
5.1.5.5
7-Ethynyl-2-(4-methoxyphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (8)
PQ 14 (150 mg, 0.39 mmol) was dissolved in 15 mL MeOH and K2CO3 (107 mg, 0.77 mmol) was added. After stirring for 2.5
h at rt the solvent was removed under reduced pressure. The residue was dissolved in DMSO, filtered through a syringe filter
(0.2 μm) and purified by HPLC to give 8 (yellow solid, 104 mg, 0.33 mmol, 85%); m.p. decomposition >300 °C; 1H NMR
(400 MHz, DMSO-d6): δ 3.78 (s, 3H), 4.47 (s, 1H), 6.97 – 7.06 (m, 2H), 7.58 (dd, J = 8.3, 1.6 Hz, 1H), 7.77 (d, J = 1.5 Hz,
1H), 8.04 – 8.10 (m, 2H), 8.18 (d, J = 8.2 Hz, 1H), 8.76 (s, 1H), 12.82 (br s, 1H);13C NMR (151 MHz, DMSO-d6): δ 55.3,
82.6, 83.0, 106.5, 113.9, 119.0, 120.4, 122.6, 122.7, 122.8, 129.1, 133.5, 135.7, 140.1, 142.0, 156.0, 161.0; HR-MS: m/z
316.1090 [M+H] + (calc. 316.1081, diff. -2.88 pm).
5.1.5.6
7-Ethyl-2-(4-methoxyphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (9)
PQ 8 (20 mg, 0.063 mmol) was dissolved in 3 mL MeOH and Pd/C (2 mg, 10 wt%) was added. The reaction mixture was
stirred at room temperature under hydrogen atmosphere (1 atm). After 3.5 h the solvent was removed under reduced pressure.
The residue was dissolved in DMSO, filtered through a syringe filter (0.2 μm) and purified by HPLC to give 9 (yellow solid,
19 mg, 0.60 mmol, 94%); m.p. decomposition >300 °C; 1H NMR (600 MHz, DMSO-d6): δ 1.26 (t, J = 7.6 Hz, 3H), 2.77 (q, J
= 7.6 Hz, 2H), 3.79 (s, 3H), 6.98 – 7.04 (m, 2H), 7.42 (dd, J = 8.2, 1.6 Hz, 1H), 7.50 – 7.53 (m, 1H), 8.10 (d, J = 9.1 Hz, 2H),
8.13 (d, J = 8.2 Hz, 1H), 8.67 (s, 1H), 12.70 (br s, 1H); 13C NMR (151 MHz, DMSO-d6): δ 15.3, 28.2, 55.2, 106.1, 113.8,
+
116.7, 118.2, 120.3, 122.1, 126.6, 133.7, 136.1, 139.4, 142.8, 146.0, 155.8, 161.1; HR-MS: m/z 320.1407 [M+H] (calc.
320.1394, diff. -4.23 ppm).
5.1.5.7
7-Acetyl-2-(4-methoxyphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (10)
PQ 8 (64 mg, 0.2 mmol) was dissolved in 1 mL CF3CH2OH. Then H2O (7.2 μL, 0.4 mmol) and CF3SO3H (62 μL, 0.7 mmol)
were added and the reaction mixture was heated to 70 °C. After 3 days the solvent was removed under reduced pressure and
the residue was dissolved in DMSO, filtered through a syringe filter (0.2 μm) and purified by HPLC to give 10 (yellow solid,
9 mg, 0.027 mmol, 14%). m.p. decomposition >300 °C; 1H NMR (400 MHz, DMSO-d6) δ 2.67 (s, 3H), 3.79 (s, 3H), 7.02 (d,
J = 9.1 Hz, 2H), 8.05 (dd, J = 8.3, 1.3 Hz, 1H), 8.10 (d, J = 9.1 Hz, 2H), 8.26 – 8.33 (m, 2H), 8.77 (s, 1H), 12.80 (br s, 1H);
13C NMR (151 MHz, DMSO-d6) δ 26.9, 55.3, 106.4, 113.9, 119.8, 120.5, 122.4, 125.2, 133.5, 137.1, 137.3 141.1, 142.1 (s,
C5a/C9b/C1’), 156.0 (s, C4’), 161.0 (s, CO), 197.0; HR-MS: m/z 334.1194 [M+H] + (calc. 334.1186, diff. -2.39 ppm).