7
24
K. V. Vani, G. Ramesh, and C. V. Rao
Vol 53
H O and tert-butanol (8 mL). The mixture was heated at 60°C for 8 h.
Synthesis of 3-unsubstituted/substituted-4-(2-cyclopropyl-
3,4-dihydro-3-substituted-4-oxoquinazolin-6-yl)benzonitrile (19,
20, 21, 22)
2
The completion of the reaction was monitored by TLC. Then, the
resulting solid was filtered, washed with water, dried and recrystallized
from chloroform to obtain pure compound 12. Yield 81%; mp 222–
4-(2-Cyclopropyl-3,4-dihydro-3-methyl-4-oxoquinazolin-6-yl)benzonitrile
223°C; IR (KBr): 3146, 2998, 2960, 2108, 1754, 1665, 1583, 1563,
2 3
(19). A total of 2M Na CO (2eq) was added to a stirred solution of 6-
1
471, 1445, 1398, 1377, 1341, 1304, 1284, 1236, 1182, 1125, 1049,
bromo-2-cyclopropyl-3-methylquinazolin-4(3H)-one 16 (1 eq)
in dioxane (2 mL) and 4-cyanophenylboronic acid 18a (1.5 eq).
ꢀ
1 1
1025, 992, 892, 878, 831, 758 cm ; H NMR (DMSO-d ): δ 1.05–
6
1
(
5
.13 (m, 4H, 2 × CH
m, 1H, CH of cyclopropyl), 4.16 (q, 2H, CH
.57 (s, 2H, CH ), 7.55 (d, 1H, Ar–H), 7.77–7.80 (dd, 1H, Ar–H),
2
of cyclopropyl), 1.20 (t, 3H, CH
3
), 2.46–2.48
3 4
Then added Pd(PPh ) (0.01 eq) while purging argon gas.
2
), 5.35 (s, 2H, CH
2
),
Reaction mixture was heated to reflux for 16 h. Progress of the
reaction was checked by TLC. Then, the resulting reaction
mixture was cooled to room temperature and diluted with water
and extracted with ethyl acetate. Organic layer was separated
and dried over Na SO . Solvent was evaporated under reduced
2 4
pressure to obtain crude compound that was purified by column
2
13
8
d
6
1
.03 (d, 1H, Ar–H), 8.13 (s, 1H, triazole proton); C NMR (DMSO-
): δ 9.09, 10.06, 13.88, 50.40, 59.84, 61.50, 120.84, 121.89, 125.09,
25.29, 128.92, 130.23, 134.54, 145.79, 158.60, 160.19, 167.07;
ꢀ
LCMS (m/z): 386 (M–H) . Anal. Calcd for C18
H
18ClN
5
O
3
: C, 55.75;
H, 4.68; N, 18.06. Found: C, 55.77; H, 4.71; N, 18.08.
chromatography using hexane:ethyl acetate (3:7) to get pure 4-(2-
cyclopropyl-3,4-dihydro-3-methyl-4-oxoquinazolin-6-yl)benzonitrile
By adopting the similar procedure used for 12, remaining com-
pounds 13, 14, 15 were synthesized.
1
(19). Yield 72%; H NMR (DMSO-d
cyclopropyl), 1.14–1.17 (m, 2H, CH
2
6
): δ 1.07–1.12 (m, 2H, CH
of cyclopropyl), 2.29–2.33 (m,
1H, CH of cyclopropyl), 3.73 (s, 3H, CH ), 7.63 (d, 1H, Ar–H), 7.93–
2
of
2
-(4-((6-Chloro-2-cyclopropyl-4-oxoquinazolin-3(4H)-yl)methyl)-
H-1,2,3-triazol-1-yl)-N-(2-methoxyphenyl)acetamide (13). Yield
4%; mp 256–257°C; IR (KBr): 3434, 3276, 3145, 3013, 2951,
664, 1583, 1555, 1495, 1470, 1435, 1396, 1338, 1322, 1286, 1265,
238, 1212, 1181, 1131, 1116, 1045, 1026, 969, 927, 899, 834, 804,
1
9
1
3
7.99 (m, 4H, Ar–H), 8.13–8.15 (dd, 1H, Ar–H), 8.38 (d, 1H, Ar–H);
+
LCMS (m/z): 302 (M + H) .
1
The same experimental procedure was used for the preparation
of remaining compounds 20, 21, 22.
ꢀ
1
1
745 cm
;
H NMR (DMSO-d
6
): δ 1.06–1.08 (m, 2H, CH
2
of
cyclopropyl), 1.14–1.16 (m, 2H, CH of cyclopropyl), 2.32–2.35 (m,
2
3-Chloro-4-(2-cyclopropyl-3,4-dihydro-3-methyl-4-oxoquinazolin-6-
1
5
H, CH of cyclopropyl), 3.84 (s, 3H, OCH
.57 (s, 2H, CH ), 6.87-6.91 (m, 1H, Ar–H), 7.05–7.09 (m, 2H,
Ar–H), 7.56 (d, 1H, Ar–H), 7.78–7.80 (dd, 1H, Ar–H), 7.90 (d,
3
), 5.39 (s, 2H, CH
2
),
1
yl)benzonitrile (20). Yield 78%; H NMR (DMSO-d
(
6
): δ 1.08–1.12
of cyclopropyl),
.28–2.32 (m, 1H, CH of cyclopropyl), 3.72 (s, 3H, CH ), 7.62 (d, 1H,
2
2 2
m, 2H, CH of cyclopropyl), 1.15–1.16 (m, 2H, CH
2
3
1
9
5
1
1
H, Ar–H), 8.04 (d, 1H, Ar–H), 8.13 (s, 1H, triazole proton),
1
3
Ar–H), 7.70 (d, 1H, Ar–H), 7.83–7.85 (dd, 1H, Ar–H), 7.92–7.94 (dd,
.66 (s, 1H, NH); C NMR (DMSO-d ): δ 9.05, 13.97, 52.16,
13
6
1
(
H, Ar–H), 8.14 (d, 1H, Ar–H), 8.21 (d, 1H, Ar–H); C NMR
DMSO-d ): δ 8.46, 14.10, 30.03, 112.03, 117.30, 119.37, 126.61,
126.66, 131.34, 132.17, 132.33, 133.32, 134.27, 134.65, 143.37,
5.65, 60.76, 111.25, 120.21, 120.88, 121.63, 124.80, 125.07,
6
25.36, 126.48, 128.91, 130.13, 134.47, 142.13, 145.79,
ꢀ
49.50, 158.62, 160.11, 164.26; LCMS (m/z): 463 (M–H) .
+
146.97, 159.34, 161.06; LCMS (m/z): 336 (M + H) .
Anal. Calcd for C H ClN O : C, 59.42; H, 4.55; N, 18.08.
2
3
21
6 3
4
-(2-Cyclopropyl-3,4-dihydro-4-oxo-3-((pyridin-3-yl)methyl)quinazolin-6-
Found: C, 59.45; H, 4.57; N, 18.13.
-(4-((6-Chloro-2-cyclopropyl-4-oxoquinazolin-3(4H)-yl)methyl)-1H-
,2,3-triazol-1-yl)-N-(3-methoxyphenyl)acetamide (14). Yield 90%;
mp 262–263°C; IR (KBr): 3436, 3276, 3148, 3014, 2951, 1666, 1583,
545, 1495, 1466, 1435, 1392, 1328, 1261, 1238, 1187, 1114, 1045,
1
yl)benzonitrile (21). Yield 70%; H NMR (DMSO-d
H, CH of cyclopropyl), 1.12–1.17 (m, 2H, CH of cyclopropyl), 2.19–
.21 (m, 1H, CH of cyclopropyl), 5.62 (s, 2H, CH ), 7.35–7.38 (m, 1H,
6
): δ 0.96–0.98 (m,
2
2
2
2
2
1
2
Ar–H), 7.67 (d, 2H, Ar–H), 7.94–8.00 (m, 4H, Ar–H), 8.18 (d, 1H, Ar–H),
.42 (s, 1H, Ar–H), 8.50 (d, 1H, Ar–H), 8.60 (s, 1H, Ar–H); LCMS (m/z):
1
ꢀ
1 1
8
1
024, 969, 896, 838, 804, 749 cm ; H NMR (DMSO-d
.08 (m, 2H, CH2 of cyclopropyl), 1.12–1.14 (m, 2H, CH2 of
cyclopropyl), 2.31–2.35 (m, 1H, CH of cyclopropyl), 3.84 (s, 3H,
OCH ), 5.38 (s, 2H, CH ), 5.56 (s, 2H, CH ), 7.11 (d, 1H, Ar–H),
.29–7.33 (m, 1H, Ar–H), 7.41 (d, 1H, Ar–H), 7.56 (d, 1H, Ar–H),
6
): δ 1.05–
+
379 (M + H) .
1
3
-Chloro-4-(2-cyclopropyl-3,4-dihydro-4-oxo-3-((pyridin-3-yl)methyl)
1
quinazolin-6-yl)benzonitrile (22). Yield 72%; H NMR (DMSO-d
0.97–0.99 (m, 2H, CH of cyclopropyl), 1.07–1.12 (m, 2H, CH
cyclopropyl), 2.19–2.20 (m, 1H, CH of cyclopropyl), 5.61 (s, 2H, CH
6
): δ
of
),
3
2
2
7
2
2
7
.72–7.77 (m, 2H, Ar–H), 8.02 (s, 1H, Ar–H), 8.13 (s, 1H, triazole
2
+
proton), 9.66 (s, 1H, NH); LCMS (m/z): 465 (M + H) . Anal. Calcd for
7.35–7.38 (m, 1H, Ar–H), 7.65–7.67 (m, 2H, Ar–H), 7.71 (d, 1H, Ar–
H), 7.87–7.90 (dd, 1H, Ar–H), 7.93–7.95 (dd, 1H, Ar–H), 8.18 (d, 1H,
Ar–H), 8.22 (s, 1H, Ar–H), 8.50 (d, 1H, Ar–H), 8.60 (s, 1H, Ar–H);
C H ClN O : C, 59.42; H, 4.55; N, 18.08. Found: C, 59.37; H, 4.57;
23
21
6 3
N, 18.12.
-(4-((6-Chloro-2-cyclopropyl-4-oxoquinazolin-3(4H)-yl)methyl)-1H-
,2,3-triazol-1-yl)-N-(3-chlorophenyl)acetamide (15). Yield 78%; mp
27–228°C; IR (KBr): 3342, 3196, 3159, 3086, 3013, 2954, 2924,
794, 1756, 1671, 1581, 1562, 1471, 1434, 1399, 1366, 1334, 1304,
+
2
LCMS (m/z): 413 (M + H) .
Synthesis of (1E)-3-unsubstituted/substituted-4-(2-cyclopropyl-3,4-
dihydro-3-substituted-4-oxoquinazolin-6-yl)-N′-hydroxybenzamidine
1
2
(
23, 24, 25, 26)
(1E)-4-(2-Cyclopropyl-3,4-dihydro-3-methyl-4-oxoquinazolin-6-yl)-N
′-hydroxybenzamidine (23). A mixture of 4-(2-cyclopropyl-3,4-
1
ꢀ
1
1
272, 1228, 1174, 1126, 1048, 988, 952, 891, 874, 834, 794, 756 cm ;
1
H NMR (DMSO-d
.34–2.38 (m, 1H, CH of cyclopropyl), 5.33 (s, 2H, CH
CH ), 7.14 (d, 1H, Ar–H), 7.33–7.37 (m, 1H, Ar–H), 7.43 (d, 1H, Ar–
H), 7.56 (d, 1H, Ar–H), 7.75–7.80 (m, 2H, Ar–H), 8.04 (s, 1H, Ar–H),
6
): δ 1.07–1.14 (m, 4H, 2 × CH
2
of cyclopropyl),
), 5.58 (s, 2H,
2
2
dihydro-3-methyl-4-oxoquinazolin-6-yl)benzonitrile 19 (0.0016 mol) and
hydroxyl amine hydrochloride (0.0024 mol) in THF (3 mL) was
refluxed for 8 h. Then, the resulting mixture was dissolved in ethyl
acetate, and the solvent was concentrated under reduced pressure to give
crude residue that was purified by column chromatography using
hexane : ethyl acetate as eluent to obtain pure compound 23. Yield 61%;
2
13
8
.16 (s, 1H, triazole proton), 10.67 (s, 1H, NH); C NMR (DMSO-d6):
δ 9.56, 14.47, 52.64, 52.92, 118.08, 119.17, 121.38, 123.92, 125.57,
25.90, 129.41, 130.65, 131.04, 133.60, 134.98, 140.24, 142.67, 146.29,
1
+
1
159.10, 160.62, 164.99; LCMS (m/z): 469 (M + H) . Anal. Calcd for
H NMR (DMSO-d ): δ 1.06–1.11 (m, 2H, CH of cyclopropyl), 1.14–
6
2
C H Cl N O : C, 56.30; H, 3.87; N, 17.91. Found: C, 56.32; H, 3.86;
1.16 (m, 2H, CH2 of cyclopropyl), 2.28–2.33 (m, 1H, CH of
22
18
2 6 2
N, 17.94.
cyclopropyl), 3.73 (s, 3H, CH ), 5.84 (s, 2H, NH ), 7.60 (d, 1H, Ar–H),
3
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet