Journal of Medicinal Chemistry
Article
1
yield: 12.3%; mp 154−155 °C; purity: 98.2%; H NMR (600 MHz,
1H, quinazolone-6-H), 7.68 (d, J = 6.3 Hz, 1H, indole-4-H), 7.59 (s,
1
3
CDCl ): δ 9.09 (s, 1H, quinazolone-2-H), 8.23 (d, J = 8.5 Hz, 1H,
quinazolone-5-H), 7.94 (d, J = 2.9 Hz, 1H, thiazole-5-H), 7.70 (t, J =
1H, CCH), 7.26 (s, 2H, indole-5,7-H) ppm; C NMR (150 MHz,
3
DMSO-d ): δ 177.54, 167.24, 159.70, 150.14, 149.68, 145.66, 140.22,
6
7
.5 Hz, 3H, thiazole-4-H, quinazolone-8-H, CCH), 7.47 (d, J = 8.5
Hz, 1H, quinazolone-6-H), 7.08 (s, 1H, Ph-3-H), 6.96 (d, J = 7.9 Hz,
H, Ph-6-H), 6.82 (d, J = 7.9 Hz, 1H, Ph-5-H), 2.43 (s, 3H, Ph-2-
138.02, 136.98, 131.66, 129.13, 128.43, 128.32, 128.19, 127.32,
126.77, 126.67, 122.50, 121.54, 119.97, 113.07, 109.29 ppm; HRMS
+
1
(ESI): calcd for C H Cl N O S [M + H] , 467.0136; found,
2
2
12
2
4
2
1
3
CH ), 2.27 (s, 3H, Ph-4-CH ) ppm; C NMR (150 MHz, CDCl ): δ
467.0128.
3
3
3
1
1
1
78.48, 166.17, 160.58, 148.94, 147.69, 144.75, 142.55, 141.34,
40.88, 138.77, 132.26, 131.65, 128.49, 127.98, 127.91, 127.79,
Z-7-Chloro-3-(1-(6-methyl-1H-indol-3-yl)-3-oxo-3-(thiazol-2-yl)-
prop-1-en-2-yl)quinazolin-4(3H)-one (6c). The preparative process
of compound 4a was slightly altered to provide compound 6c with 6-
methylindole-3-carboxaldehyde (125 mg, 0.78 mmol) and quinazo-
lonthiazole 3 (200 mg, 0.65 mmol) as initial reactants. Red solid (103
27.35, 127.21, 126.47, 120.58, 21.24, 19.99 ppm; HRMS (ESI):
+
calcd for C H ClN O S [M + H] , 422.0730; found, 422.0724.
22
16
3
2
Z-7-Chloro-3-(1-(4-methoxyphenyl)-3-oxo-3-(thiazol-2-yl)prop-
-en-2-yl)quinazolin-4(3H)-one (5m). The preparative process of
1
1
mg); yield: 35.2%; mp >250 °C; purity: 97.2%; H NMR (600 MHz,
compound 4a was slightly altered to provide compound 5m with 4-
DMSO-d ): δ 11.94 (s, 1H, NH), 9.64 (s, 1H, quinazolone-2-H), 8.34
6
methoxybenzaldehyde (107 mg, 0.78 mmol) and quinazolonthiazole
(s, 1H, indole-2-H), 8.25−8.20 (m, 3H, quinazolone-5-H, thiazole-
4,5-H), 7.92 (s, 1H, quinazolone-8-H), 7.68 (d, J = 8.0 Hz, 1H,
quinazolone-6-H), 7.60 (d, J = 7.8 Hz, 1H, indole-4-H), 7.30 (s, 1H,
CCH), 7.13 (s, 1H, indole-7-H), 7.06 (d, J = 7.7 Hz, 1H, indole-5-
H), 2.41 (s, 3H, CH ) ppm; C NMR (150 MHz, DMSO-d ): δ
3 6
3
(200 mg, 0.65 mmol) as initial reactants. Yellow solid (76 mg);
1
yield: 27.4%; mp 179−180 °C; purity: 99.6%; H NMR (600 MHz,
CDCl ): δ 9.02 (s, 1H, quinazolone-2-H), 8.26 (d, J = 8.5 Hz, 1H,
3
1
3
quinazolone-5-H), 7.95 (s, 1H, thiazole-5-H), 7.85 (s, 1H,
quinazolone-8-H), 7.79 (s, 1H, CCH), 7.68 (d, J = 3.0 Hz, 1H,
thiazole-4-H), 7.50 (d, J = 8.5 Hz, 1H, quinazolone-6-H), 7.31 (d, J =
177.28, 167.54, 159.68, 150.41, 149.69, 145.61, 140.17, 137.03,
133.36, 130.64, 129.12, 128.28, 127.99, 127.30, 125.87, 125.70,
124.00, 121.58, 118.22, 113.06, 109.42, 21.69 ppm; HRMS (ESI):
8
3
1
1
.4 Hz, 2H, Ph-2,6-H), 6.84 (d, J = 8.2 Hz, 2H, Ph-3,5-H), 3.80 (s,
1
3
+
H, OCH ) ppm; C NMR (150 MHz, CDCl ): δ 178.43, 166.52,
calcd for C H ClN O S [M + H] , 447.0682; found, 447.0676.
3
3
23 16
4
2
62.43, 160.39, 149.21, 148.05, 144.75, 144.60, 141.05, 132.92,
Z-7-Chloro-3-(1-(1-ethyl-1H-indol-3-yl)-3-oxo-3-(thiazol-2-yl)-
prop-1-en-2-yl)quinazolin-4(3H)-one (6d). The preparative process
of compound 4a was slightly altered to provide compound 6d with 1-
ethlylindole-3-carboxaldehyde (136 mg, 0.78 mmol) and quinazolon-
thiazole 3 (200 mg, 0.65 mmol) as initial reactants. Yellow solid (152
29.56, 128.72, 128.08, 127.39, 126.43, 124.17, 120.93, 114.96, 55.43
+
ppm; HRMS (ESI): calcd for C H ClN O S [M + H] , 424.0523;
2
1
14
3
3
found, 424.0518.
Z-7-Chloro-3-(1-(2-fluoro-4-(piperidin-1-yl)phenyl)-3-oxo-3-
thiazol-2-yl)prop-1-en-2-yl) Quinazolin-4(3H)-one (5n). The prep-
1
(
mg); yield: 50.4%; mp 165−166 °C; purity: 97.0%; H NMR (600
arative process of compound 4a was slightly altered to provide
compound 5n with 2,4-difluorobenzaldehyde (112 mg, 0.78 mmol)
and quinazolonthiazole 3 (200 mg, 0.65 mmol) as initial reactants.
MHz, DMSO-d ): δ 9.63 (s, 1H, quinazolone-2-H), 8.32 (s, 1H,
6
indole-2-H), 8.27−8.16 (m, 3H, quinazolone-5-H, thiazole-4,5-H),
7.91 (s, 1H, quinazolone-8-H), 7.75 (d, J = 7.6 Hz, 1H, indole-4-H),
7.67 (d, J = 8.1 Hz, 1H, indole-7-H), 7.63 (d, J = 7.9 Hz, 1H,
quinazolone-6-H), 7.38 (s, 1H, CCH), 7.35−7.30 (m, 1H, indole-
6-H), 7.27 (t, J = 6.9 Hz, 1H, indole-5-H), 4.20 (d, J = 6.9 Hz, 2H,
1
Red solid (75 mg); yield: 23.2%; mp 141−142 °C; H NMR (600
MHz, CDCl ): δ 9.25 (s, 1H, quinazolone-2-H), 8.27 (d, J = 8.5 Hz,
3
1
H, quinazolone-5-H), 7.96 (s, 1H, thiazole-5-H), 7.87 (s, 1H, C
1
3
CH), 7.78 (s, 1H, quinazolone-8-H), 7.67−7.62 (m, 1H, thiazole-4-
H), 7.48 (d, J = 8.4 Hz, 1H, quinazolone-6-H), 6.92 (t, J = 8.6 Hz,
CH ), 1.21 (t, J = 6.7 Hz, 3H, CH ) ppm; C NMR (150 MHz,
2
3
DMSO-d ): δ 177.42, 167.51, 159.83, 150.20, 149.73, 145.59, 140.02,
6
1
H, Ph-6-H), 6.51 (d, J = 14.4 Hz, 1H, Ph-5-H), 6.45−6.40 (m, 1H,
138.12, 136.38, 133.01, 129.09, 128.47, 128.17, 128.03, 127.27,
125.99, 123.93, 122.59, 121.73, 118.84, 111.79, 108.63, 41.76, 15.32
Ph-3-H), 3.31 (s, 4H, piperidine-2,6-H), 1.63 (s, 6H, piperidine-3,4,5-
H) ppm; 13C NMR (150 MHz, CDCl ): δ 177.98, 166.86, 164.97,
ppm; HRMS (ESI): calcd for C H ClN O S [M + H] , 461.0839;
+
3
24 17
4
2
1
1
1
63.29, 160.23, 154.52, 149.15, 148.30, 144.60, 140.75, 137.21,
30.31, 130.29, 128.65, 127.90, 127.80, 127.20, 125.89, 120.94,
found, 461.0833.
Z-3-(1-(Benzo[b]thiophen-3-yl)-3-oxo-3-(thiazol-2-yl)prop-1-en-
2-yl)-7-chloroquinazolin-4(3H)-one (6e). The preparative process of
compound 4a was slightly altered to provide compound 6e with
benzothiophene-3-carboxaldehyde (127 mg, 0.78 mmol) and
quinazolonthiazole 3 (200 mg, 0.65 mmol) as initial reactants. Yellow
solid (179 mg); yield: 60.8%; mp 237−238 °C; purity: 99.8%; H
NMR (600 MHz, DMSO-d ): δ 9.40 (s, 1H, quinazolone-2-H),
10.26, 100.04, 99.85, 48.17, 25.10, 24.06 ppm; HRMS (ESI): calcd
+
for C H ClFN O S [M + H] , 495.1058; found, 495.1051.
25
20
4
2
Z-3-(1-(1H-Indol-3-yl)-3-oxo-3-(thiazol-2-yl)prop-1-en-2-yl)-7-
chloroquinazolin-4(3H)-one (6a). The preparative process of
compound 4a was slightly altered to provide compound 6a with
indol-3-aldehyde (114 mg, 0.78 mmol) and quinazolonthiazole 3
1
6
(
200 mg, 0.65 mmol) as initial reactants. Yellow solid (136 mg);
8.36−8.30 (m, 2H, benzothiophene-4-H, benzothiophene-7-H), 8.24
(s, 1H, benzothiophene-2-H), 8.19 (d, J = 8.4 Hz, 1H, quinazolone-5-
H), 8.10 (d, J = 7.9 Hz, 1H, thiazole-5-H), 8.08 (d, J = 7.9 Hz, 1H,
thiazole-4-H), 7.88 (s, 1H, quinazolone-8-H), 7.85 (s, 1H, CCH),
7.68 (d, J = 8.1 Hz, 1H, quinazolone-6-H), 7.57 (t, J = 7.3 Hz, 1H,
benzothiophene-6-H), 7.51 (t, J = 7.2 Hz, 1H, benzothiophene-5-H)
1
yield: 48.0%; mp >250 °C; purity: 98.7%; H NMR (600 MHz,
DMSO-d ): δ 12.05 (s, 1H, NH), 9.68 (s, 1H, quinazolone-2-H), 8.36
6
(
s, 1H, indole-2-H), 8.25 (d, J = 6.6 Hz, 2H, quinazolone-5-H,
thiazole-5-H), 8.22 (d, J = 8.5 Hz, 1H, thiazole-4-H), 7.92 (s, 1H,
quinazolone-8-H), 7.76 (d, J = 7.6 Hz, 1H, indole-4-H), 7.68 (d, J =
7
7
1
3
.3 Hz, 1H, quinazolone-6-H), 7.53 (d, J = 7.8 Hz, 1H, indole-7-H),
ppm; C NMR (150 MHz, DMSO-d ): δ 178.65, 166.26, 160.00,
6
1
3
.29−7.23 (m, 2H, indole-5,6-H), 7.21 (s, 1H, CCH) ppm;
C
149.55, 149.19, 145.95, 140.25, 139.40, 138.64, 135.09, 133.96,
131.83, 129.09, 128.36, 127.35, 127.26, 126.07, 125.91, 123.72,
121.89, 121.29 ppm; HRMS (ESI): calcd for C H ClN O S [M +
NMR (150 MHz, DMSO-d ): δ 177.35, 167.46, 159.66, 150.33,
6
1
1
1
49.69, 145.62, 140.16, 138.73, 136.54, 130.89, 129.11, 128.28,
28.05, 127.88, 127.30, 126.09, 123.90, 122.30, 121.58, 118.45,
13.34, 109.36 ppm; HRMS (ESI): calcd for C H ClN O S [M +
2
2
12
3
2 2
+
H] , 450.0138; found, 450.0132.
Z-7-Chloro-3-(1-(naphthalen-2-yl)-3-oxo-3-(thiazol-2-yl)prop-1-
en-2-yl)quinazolin-4(3H)-one (7). The preparative process of
compound 4a was slightly altered to provide compound 7 with 2-
naphthaldehyde (123 mg, 0.78 mmol) and quinazolonthiazole 3 (200
2
2
12
4
2
+
H] , 433.0526; found, 433.0520.
Z-7-Chloro-3-(1-(6-chloro-1H-indol-3-yl)-3-oxo-3-(thiazol-2-yl)
Prop-1-en-2-yl)quinazolin-4(3H)-one (6b). The preparative process
of compound 4a was slightly altered to provide compound 6b with 6-
chloroindole-3-carboxaldehyde (141 mg, 0.78 mmol) and quinazo-
lonthiazole 3 (200 mg, 0.65 mmol) as initial reactants. Red solid (75
mg); yield: 24.5%; mp > 250 °C; purity: 98.9%; H NMR (600 MHz,
DMSO-d ): δ 12.05 (s, 1H, NH), 9.58 (s, 1H, quinazolone-2-H), 8.35
mg, 0.65 mmol) as initial reactants. Yellow solid (89 mg); yield:
1
30.1%; mp 128−129 °C; purity: 98.2%; HNMR (600 MHz, CDCl ):
3
δ 9.14 (s, 1H, quinazolone-2-H), 8.28 (d, J = 8.5 Hz, 1H,
quinazolone-5-H), 7.98 (d, J = 3.0 Hz, 1H, thiazole-5-H), 7.96 (s,
1H, naphthalene-1-H), 7.84 (s, 1H, quinazolone-8-H), 7.78 (dd, J =
4.7, 2.8 Hz, 2H, quinazolone-6-H, naphthalene-8-H), 7.74 (d, J = 8.0
Hz, 1H, naphthalene-5-H), 7.73−7.70 (m, 2H, thiazole-4-H,
1
6
(
s, 1H, indole-2-H), 8.24 (d, J = 19.9 Hz, 3H, quinazolone-5-H,
thiazole-4,5-H), 7.92 (s, 1H, quinazolone-8-H), 7.77 (d, J = 6.9 Hz,
7
641
J. Med. Chem. 2021, 64, 7630−7645