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2.55 (s, 3H, CH3), 3.38 (s, 3H, NCH3), 4.78 (s, 2H, CH2), 6.74 (s, 1H,
ArH), 7.17 (s, 1H, ArH), 7.22–7.41 (m, 5H, ArH), 7.69–7.74 (m, 3H,
ArH). API-ES m/z: 400.1 (MH+). Anal. (C23H21N5S) C, H, N.
4.1.4.6. (E)-8-Methoxy-2-methyl-5-(2-(1-methyl-4-phenyl-1H-
imidazol-2-yl)vinyl)pyrazolo[1,5-c]quinazoline 8f. Yield 82%.
1H NMR (CDCl3) d 2.56 (s, 3H, CH3), 3.89 (s, 3H, NCH3), 3.94 (s,
3H, OCH3), 6.65 (s, 1H, ArH), 7.08–7.89 (m, 9H, ArH), 8.12 (d, 1H,
J = 15.6 Hz, CH), 8.50 (d, 1H, J = 15.6 Hz, CH). API-ES m/z: 396.1
(MH+).
4.1.3.8. 2,9-Dimethyl-5-((1-methyl-4-phenyl-1H-imidazol-2-yl-
thio)methyl)pyrazolo[1,5-c]quinazoline 1h. Yield 70%. Mp
155 °C (AcOEt/iPr2O). 1H NMR (CDCl3) d 2.49 (s, 3H, CH3), 2.52 (s,
3H, CH3), 3.43 (s, 3H, NCH3), 4.76 (s, 2H, CH2), 6.72 (s, 1H, ArH),
7.18 (s, 1H, ArH), 7.21–7.41 (m, 5H, ArH), 7.66–7.71 (m, 3H, ArH).
API-ES m/z: 400.1 (MH+). Anal. (C23H21N5S) C, H, N.
4.1.4.7. (E)-9-Methoxy-2-methyl-5-(2-(1-methyl-4-phenyl-1H-
imidazol-2-yl)vinyl)pyrazolo[1,5-c]quinazoline 8g. Yield 72%.
1H NMR (CDCl3) d 2.58 (s, 3H, CH3), 3.88 (s, 3H, NCH3), 3.94 (s,
3H, OCH3), 6.74 (s, 1H, ArH), 7.18–7.44 (m, 6H, ArH), 7.80–7.89
(m, 3H, ArH), 8.06 (d, 1H, J = 15.6 Hz, CH), 8.49 (d, 1H, J = 15.6 Hz,
CH). API-ES m/z: 396.1 (MH+).
4.1.4. General procedure IV. Synthesis of (E)-2-methyl-5-(2-(1-
methyl-4-phenyl-1H-imidazol-2-yl)vinyl)pyrazolo[1,5-c]quin-
azolines 8a–i
4.1.4.8. (E)-2,7-Dimethyl-5-(2-(1-methyl-4-phenyl-1H-imidazol-
2-yl)vinyl)pyrazolo[1,5-c]quinazoline 8h. Yield 40%. 1H NMR
(CDCl3) d 2.58 (s, 3H, CH3), 2.79 (s, 3H, CH3), 3.93 (s, 3H, NCH3),
6.77 (s, 1H, ArH), 7.26–7.44 (m, 6H, ArH), 7.78–7.89 (m, 3H, ArH),
8.24 (d, 1H, J = 15.4 Hz, CH), 8.46 (d, 1H, J = 15.6 Hz, CH). API-ES
m/z: 380.1 (MH+).
A mixture of 5-(chloromethyl)-2-methylpyrazolo[1,5-c]quinaz-
oline 4 (1 equiv, 0.95 mmol) and triphenylphosphine (1 equiv,
0.95 mmol) in CH3CN (4 ml) was heated at 80 °C for 5 h. The solution
was concentrated and the residue triturated with THF, filtered and
dried to give the desired ((2-methylpyrazolo[1,5-c]quinazolin-5-
yl)methyl)triphenylphosphonium chloride 6 in almost quantitative
yields as white solid, which was used without characterisation.
To a suspension of 60% NaH in mineral oil (1.1 equiv, 0.88 mmol)
in DMF (4 ml) cooled to ꢁ5 °C, the phosphonium salt 6 (1 equiv,
0.76 mmol) was portionwise added and the resulting yellow solu-
tion stirred for 300 at the same temperature. 1-Methyl-4-phenyl-
1H-imidazole-2-carbaldehyde 7 (1 equiv, 0.76 mmol) was portion-
wise added and the resulting mixture stirred at room temperature
for 1.5 h. The whole was poured onto H2O, extracted with CH2Cl2
and the combined organic layers dried and concentrated. The resi-
due was purified by FC (petroleum ether/AcOEt 6:4, 1:1, AcOEt) to
give the pure product as a yellow solid.
4.1.4.9. (E)-2,9-Dimethyl-5-(2-(1-methyl-4-phenyl-1H-imidazol-
2-yl)vinyl)pyrazolo[1,5-c]quinazoline 8i. Yield 75%. 1H NMR
(CDCl3) d 2.53 (s, 3H, CH3), 2.58 (s, 3H, CH3), 3.90 (s, 3H, NCH3),
6.75 (s, 1H, ArH), 7.26–7.44 (m, 6H, ArH), 7.73–7.89 (m, 3H, ArH),
8.12 (d, 1H, J = 15.6 Hz, CH), 8.52 (d, 1H, J = 15.8 Hz, CH). API-ES
m/z: 380.1 (MH+).
4.1.5. General procedure V. Method A. Synthesis of 2-methyl-5-
(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethyl)pyrazolo[1,5-c]-
quinazolines 1i,m–q
A mixture of the appropriate (E)-2-methyl-5-(2-(1-methyl-4-
phenyl-1H-imidazol-2-yl)vinyl)pyrazolo[1,5-c]quinazoline 8 (1 equiv,
0.76 mmol) and 10% Pd/C (0.1 equiv, 0.071 mmol) in THF (35 ml)
was hydrogenated at room temperature at 45 psi for 6 h. The sus-
pension was filtered over CeliteÒ and the solution concentrated.
Analytically pure product was isolated after purification by FC
(petroleum ether/AcOEt 1:1, 2:8, AcOEt) and trituration with
AcOEt.
4.1.4.1. (E)-2-Methyl-5-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)-
vinyl)pyrazolo[1,5-c]quinazoline 8a. Yield 60%. 1H NMR (CDCl3) d
2.58 (s, 3H, CH3), 3.89 (s, 3H, NCH3), 6.77 (s, 1H, ArH), 7.25 (s, 1H,
ArH), 7.30–7.64 (m, 5H, ArH), 7.86–7.94 (m, 4H, ArH), 8.13 (d, 1H,
J = 15.6 Hz, CH), 8.53 (d, 1H, J = 15.6, CH). API-ES m/z: 366.1 (MH+).
4.1.4.2. (E)-7-Chloro-2-methyl-5-(2-(1-methyl-4-phenyl-1H-imi-
dazol-2-yl)vinyl)pyrazolo[1,5-c]quinazoline 8b. Yield 80%. 1H
NMR (CDCl3) d 2.59 (s, 3H, CH3), 3.92 (s, 3H, NCH3), 6.80 (s, 1H,
ArH), 7.26–7.42 (m, 5H, ArH), 7.69 (d, 1H, J = 7.8 Hz, ArH), 7.82–
7.89 (m, 3H, ArH), 8.28 (d, 1H, J = 15.4 Hz, CH), 8.52 (d, 1H,
J = 15.4 Hz, CH). API-ES m/z: 400.1 (MH+).
4.1.5.1. 2-Methyl-5-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)-
ethyl)pyrazolo[1,5-c]quinazoline 1i. Yield 50%. Mp 151–153 °C.
1H NMR (CDCl3) d 2.54 (s, 3H, CH3), 3.44 (t, 2H, J = 7.0 Hz, CH2),
3.78 (s, 3H, NCH3), 3.84 (t, 2H, J = 7.0 Hz, CH2), 6.77 (s, 1H, ArH),
7.08 (s, 1H, ArH), 7.18–7.37 (m, 3H, ArH), 7.51–7.96 (m, 6H, ArH).
API-ES m/z: 368.1 (MH+). Anal. (C23H21N5) C, H, N.
4.1.4.3. (E)-8-Chloro-2-methyl-5-(2-(1-methyl-4-phenyl-1H-imi-
dazol-2-yl)vinyl)pyrazolo[1,5-c]quinazoline 8c. Yield 40%. 1H
NMR (CDCl3) d 2.57 (s, 3H, CH3), 3.90 (s, 3H, NCH3), 6.75 (s, 1H,
ArH), 7.25–7.44 (m, 6H, ArH), 7.81–7.89 (m, 3H, ArH), 8.12 (d,
1H, J = 15.4 Hz, CH), 8.50 (d, 1H, J = 15.4 Hz, CH). API-ES m/z:
400.1 (MH+).
4.1.5.2. 7-Methoxy-2-methyl-5-(2-(1-methyl-4-phenyl-1H-imi-
dazol-2-yl)ethyl)pyrazolo[1,5-c]quinazoline 1m. Yield 40%. Mp
203–205 °C. 1H NMR (CDCl3) d 2.45 (s, 3H, CH3), 3.47 (t, 2H,
J = 7.2 Hz, CH2), 3.77 (s, 3H, NCH3), 3.90 (t, 2H, J = 7.2 Hz, CH2),
3.96 (s, 3H, OCH3), 6.68 (s, 1H, ArH), 7.01 (m, 1H, ArH), 7.19 (s,
1H, ArH), 7.24–7.70 (m, 7H, ArH). API-ES m/z: 398.1 (MH+). Anal.
(C24H23N5O) C, H, N.
4.1.4.4. (E)-9-Chloro-2-methyl-5-(2-(1-methyl-4-phenyl-1H-imi-
dazol-2-yl)vinyl)pyrazolo[1,5-c]quinazoline 8d. Yield 90%. 1H
NMR (CDCl3) d 2.58 (s, 3H, CH3), 3.89 (s, 3H, NCH3), 6.75 (s, 1H,
ArH), 7.26–7.56 (m, 6H, ArH), 7.78–7.89 (m, 3H, ArH), 8.10 (d,
1H, J = 15.6 Hz, CH), 8.53 (d, 1H, J = 15.6 Hz, CH). API-ES m/z:
400.1 (MH+).
4.1.5.3. 8-Methoxy-2-methyl-5-(2-(1-methyl-4-phenyl-1H-imi-
dazol-2-yl)ethyl)pyrazolo[1,5-c]quinazoline 1n. Yield 58%. Mp
188–192 °C. 1H NMR (CDCl3) d 2.52 (s, 3H, CH3), 3.43 (t, 2H,
J = 6.8 Hz, CH2), 3.73 (s, 3H, NCH3), 3.82 (t, 2H, J = 6.8 Hz, CH2),
3.94 (s, 3H, OCH3), 6.64 (s, 1H, ArH), 7.09 (s, 1H, ArH), 7.10–7.37
(m, 6H, ArH), 7.72 (d, 1H, J = 6.8 Hz, ArH), 7.84 (d, 1H, J = 7.2 Hz,
ArH). API-ES m/z: 398.1 (MH+). Anal. (C24H23N5O) C, H, N.
4.1.4.5. (E)-7-Methoxy-2-methyl-5-(2-(1-methyl-4-phenyl-1H-
imidazol-2-yl)vinyl)pyrazolo[1,5-c]quinazoline 8e. Yield 95%.
1H NMR (CDCl3) d 2.59 (s, 3H, CH3), 3.91 (s, 3H, NCH3), 4.09 (s,
3H, OCH3), 6.77 (s, 1H, ArH), 7.07–7.89 (m, 9H, ArH), 8.21 (d, 1H,
J = 15.6 Hz, CH), 8.55 (d, 1H, J = 15.6 Hz, CH). API-ES m/z: 396.1
(MH+).
4.1.5.4. 9-Methoxy-2-methyl-5-(2-(1-methyl-4-phenyl-1H-imi-
dazol-2-yl)ethyl)pyrazolo[1,5-c]quinazoline 1o. Yield 71%. Mp
194–196 °C. 1H NMR (CDCl3) d 2.52 (s, 3H, CH3), 3.41 (t, 2H,