V. J. Ram et al. / Bioorg. Med. Chem. 11 (2003) 2439–2444
2443
.
C12H14N4O2 HCl: C, 50.98, H, 5.35, N, 19.82. Found:
C, 50.76, H, 5.55, N, 19.94.
6-Methyl-2-pyrrolidin-1-yl-3H-quinazolin-4-one
(4k).
Yield 86%; mp >250 ꢀC; MS (EI) m/z 229 (M+, 79.2),
201 (48.1), 200 (100.0), 133 (22.8); IR (KBr) 1672 cmꢂ1
1
6-Methoxy-2-piperazin-1-yl-3H-quinazolin-4-one hydro-
chloride (4e). Yield 75%; mp >250 ꢀC; MS (EI) m/z
260 (M+, 41.4), 230 (14.4), 218 (25.5), 205 (26.9), 204
(100.0); IR (KBr) 1671 cmꢂ1 (CO); 1H NMR (200 MHz,
DMSO-d6) d 2.60 (t, J=4.6 Hz, 4H, NCH2), 3.66 (t,
J=4.6 Hz, H, NCH2), 3.92 (s, 3H, OCH3), 7.10–7.12
(m, 2H, ArH), 7.17–7.20 (m, 1H, ArH), Anal. calcd for
(CO); H NMR (200 MHz, CDCl3) d 2.02–2.09 (m, 4H,
CH2), 2.39 (s, 3H, CH3), 3.61 (t, J=6.66 Hz, 4H,
NCH2), 7.28–7.44 (m, 2H, ArH), 7.86–7.88 (m, 1H,
ArH). Anal. calcd for C13H15N3O: C, 68.10, H, 6.59, N,
18.33. Found: C, 68.26, H, 6.43, N, 18.39.
6-Hydroxy-2-pyrrolidin-1-yl-3H-quinazolin-4-one
(4l).
C13H16N4O2 HCl: C, 52.62, H, 5.77, N, 18.88. Found:
C, 52.77, H, 5.89, N, 19.13.
Yield 79%; mp >250 ꢀC; MS (EI) m/z 231 (M+, 93.7),
202 (100.0), 161 (14.1), 135 (18.3); IR (KBr) 1673 cmꢂ1
(CO); 1H NMR (200 MHz, CDCl3 and DMSO-d6) d
2.01–2.03 (m, 4H, CH2), 3.57 (t, J=6.66 Hz, 4H, NCH2),
7.13 (dd, J=9.2, 2.8 Hz, 1H, ArH), 7.26 (d, J=9.2 Hz,
1H, ArH), 7.47 (d, J=2.8 Hz, 1H, ArH), 8.90 (brs, 1H,
OH). Anal. calcd for C12H13N3O2: C, 62.23, H, 5.67, N,
18.17. Found: C, 62.40, H, 5.79, N, 18.30.
.
7-Chloro-2-piperazin-1-yl-3H-quinazolin-4-one
hydro-
chloride (4f). Yield 80%; mp >250 ꢀC; MS (EI) m/z
264 (M+, 16.0), 224 (25.1), 209 (51.4), 197 (100.0); IR
(KBr) 1679 cmꢂ1 (CO); 1H NMR (200 MHz, DMSO-d6)
d 2.60 (t, J=4.6 Hz, 4H, NCH2), 3.56 (t, J=4.6 Hz, 4H,
NCH2), 7.17 (dd, J=9.2, 2.8 Hz, 1H, ArH), 7.19–7.20
(m, 1H, ArH), 7.90 (d, J=9.2 Hz, 1H, ArH). Anal.
6-Acetoxy-2-pyrrolidin-1-yl-3H-quinazolin-4-one (4m).
Yield 81%; mp >250 ꢀC; MS (EI) m/z 273 (M+, 18.3),
230 (100.0), 229 (36.2), 202 (86.0); IR (KBr) 1666.0 (CO),
.
calcd for C12H13ClN4O HCl: C, 47.86, H, 4.69, N,
18.60. Found: C, 47.59, H, 4.77, N, 18.73.
1
1757 cmꢂ1 (CO); H NMR (200 MHz, CDCl3 ) d 2.03–
6-Methyl-2-(4-methyl-piperazin-1-yl)-3H-quinazolin-4-one
(4g). Yield 71%; mp >250 ꢀC; MS (EI) m/z 258 (M+,
68.3), 201 (24.0), 188 (100.0); IR (KBr) 1676.0 cmꢂ1
(CO); 1H NMR (200 MHz, CDCl3) d 2.38 (s, 3H,
NCH3), 2.41 (s, 3H, CH3), 2.59 (t, J=4.6 Hz, 4H,
NCH2), 3.75 (t, J=4.6 Hz, 4H, NCH2), 7.41–7.42 (m,
1H, ArH), 7.54–7.59 (m, 1H, ArH), 7.86–8.02 (m, 1H,
ArH). Anal. calcd for C14H18N4O: C, 65.09, H, 7.02, N,
21.69. Found: C, 65.21, H, 7.15, N, 21.82.
2.04 (m, 4H, CH2), 2.31 (s, 3H, CH3), 3.61 (t, J=6.66 Hz,
4H, NCH2), 7.28–7.36 (m, 2H, ArH), 7.74 (d, J=2.8 Hz,
1H, ArH). Anal. calcd for C14H15N3O3: C, 61.53, H,
5.53, N, 15.38. Found: C, 61.44, H, 5.71, N, 15.25.
6-Chloro-2-pyrrolidin-1-yl-3H-quinazolin-4-one
(4n).
Yield 89%; mp >250 ꢀC; MS (EI) m/z 249 (M+, 95.0),
222 (52.0), 219 (100.0), 195 (35.5); IR (KBr) 1676 cmꢂ1
1
(CO); H NMR (200 MHz, CDCl3) d 2.04–2.11 (m, 4H,
CH2), 3.62 (t, J=6.66 Hz, 4H, NCH2), 7.31 (d,
J=9.2 Hz, 1H, ArH), 7.49 (dd, J=9.2, 2.8 Hz, 1H,
ArH), 8.08 (d, J=2.8 Hz, 1H, ArH). Anal. calcd for
C12H12ClN3O: C, 57.72, H, 4.84, N, 16.83. Found: C,
57.96, H, 4.72, N, 16.70.
6-Chloro-2-(4-methyl-piperazin-1-yl)-3H-quinazolin-4-one
(4h). Yield 77%; mp >250 ꢀC; MS (EI) m/z 278 (M+,
17.90), 221 (10.4), 208 (43.3); IR (KBr) 1679 cmꢂ1 (CO);
1H NMR (200 MHz, DMSO-d6) d 2.37 (s, 3H, NCH3),
2.62 (t, J=4.6 Hz, 4H, NCH2), 3.62 (t, J=4.6 Hz, 4H,
NCH2), 7.26 (d, J=9.2 Hz, 1H, ArH), 7.53 (dd, J=9.2,
2.8 Hz, 1H, ArH), 7.81 (d, J=2.8 Hz, 1H, ArH). Anal.
calcd for C13H15ClN4O: C, 56.02, H, 5.42, N, 20.10.
Found: C, 56.23, H, 5.56, N, 20.30.
7-Chloro-2-pyrrolidin-1-yl-3H-quinazolin-4-one
(4o).
Yield 77%; mp >250 ꢀC; MS (FAB) 250 (M+ +1,
1
100.0); IR (KBr) 1683 cmꢂ1 (CO); H NMR (200 MHz,
CDCl3 ) d 2.07–2.08 (m, 4H, CH2), 3.65 (t, J=6.66 Hz,
4H, NCH2), 7.06 (dd, J=9.2, 2.8 Hz, 1H, ArH), 7.27 (d,
J=2.8 Hz, 1H, ArH), 7.96 (dd, J=9.2, 2.8 Hz, 1H,
ArH). Anal. calcd for C12H12ClN3O: C, 57.72, H, 4.84,
N, 16.83. Found: C, 57.66, H, 4.89, N, 16.55.
6-Hydroxy-2-(4-methyl-piperazin-1-yl)-3H-quinazolin-4-
one (4i). Yield 80%; mp >250 ꢀC; MS (EI) m/z 260 (M+,
19.4), 202 (8.8), 190 (94.8); IR (KBr) 1662 (CO),
3642cmꢂ1 (OH); 1H NMR (200MHz, DMSO-d6) d 2.24
(s, 3H, NCH3), 2.45 (t, J=4.6 Hz, 4H, NCH2), 3.60 (t,
J=4.6Hz, 4H, NCH2), 7.10–7.14 (m, 2H, ArH), 7.25–
7.26 (m, 1H, ArH). Anal. calcd for C13H16N4O2: C, 59.99,
H, 6.20, N, 21.52. Found: C, 59.86, H, 6.33, N, 21.40.
7-Chloro-2-piperadin-1-yl-3H-quinazolin-4-one
(4p).
Yield 83%; mp 242 ꢀC; MS (EI) m/z 263 (M+, 100.0),
234 (73.1), 208 (39.4); IR (KBr) 1668 cmꢂ1 (CO); H
1
NMR (200 MHz, CDCl3 ) d 1.71–1.72 (m, 6H, CH2),
3.71–7.20 (m, 4H, NCH2), 7.06 (dd, J=9.2, 2.8 Hz, 1H,
ArH), 7.36 (d, J=2.8 Hz, 1H, ArH), 7.94 (d, J=9.2 Hz,
1H, ArH). Anal. calcd for C13H14ClN3O: C, 59.21, H,
5.35, N, 15.93. Found: C, 59.45, H, 5.61, N, 15.99.
4-(4-Oxo-3,4-dihydro-quinazolin-2-yl)piperazine-1-carbox-
ylic acid ethyl ester (4j). Yield 72%; mp >250 ꢀC; MS
(EI) m/z 302 (M+, 52.6), 233 (15.1), 199 (13.7), 186
(52.7), 173 (100); IR (KBr) 1598 (CO), 1676 cmꢂ1 (CO);
1H NMR (200 MHz, CDCl3) d 1.27 (t, J=4.6 Hz, 3H,
CH3), 3.66 (t, J=4.6 Hz, 4H, NCH2), 3.79 (t, J=4.6 Hz,
4H, NCH2), 4.14–4.19 (m, 2H, CH2), 7.19–7.26 (m, 1H,
ArH), 7.37 (d, J=9.2 Hz, 1H, ArH), 7.60–68 (m, 1H,
ArH), 8.07 (d, J=9.2 Hz, 1H, ArH). Anal. calcd for
C15H18N4O3: C, 59.59, H, 6.00, N, 18.53. Found: C,
59.71, H, 6.09, N, 18.67.
General procedure of 4-sec-amino-2-chloroquinazolines
(5a–b)
2,4-Dichloroquinazolines (2, 2 mmol) was refluxed for
with N1,N1-diethyl-pentane-1,4-diamine (4 mmol) in
alcohol (5 mL) for 6 h. After completion of the reaction
solvent was evaporated under reduced pressure, crude