5488 Journal of Medicinal Chemistry, 2010, Vol. 53, No. 15
Mosley et al.
7.76 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 7.3
Hz, 2H), 7.25 (d, J = 8.3 Hz, 1H), 6.32 (d, J = 15.6 Hz, 1H), 3.90
(s, 3H), 2.27 (s, 6H). 13C NMR (100 MHz, DMSO-d6) δ 168.81,
168.76, 161.5, 158.6, 149.4, 143.3, 143.0, 142.5, 141.5, 137.2,
134.4, 132.3, 131.3, 130.0, 129.8, 126.3, 125.1, 124.9, 123.4,
123.3, 122.0, 121.6, 107.2, 56.4, 21.02, 20.98. HRMS calcd for
C28H22N2O8, 515.1510 [M]þ; found, 515.14526 [M]þ. Anal.
(C28H22N2O8) C, H, N. MP 247-252 °C.
(E)-3-(6-Methoxy-2-(3-nitrostyryl)-4-oxoquinazolin-3(4H)-yl)-
benzoic Acid (77). Compound 77 was prepared via procedure C
using compound 76a (0.194 g, 0.626 mmol) and meta-nitroben-
zaldehyde (0.126 g, 0.833 mmol, 1.3 equiv) to yield the title
compound as a yellow solid (0.087 g, 33%). 1H NMR (400
MHz, DMSO-d6) δ 13.32 (bs, 1H), 8.21 (s, 1H), 8.13-8.15
(mult, 2H), 8.03 (s, 1H), 7.92 (d, J = 15.7 Hz, 1H), 7.82 (d, J =
7.8 Hz, 1H), 7.73-7.77 (mult, 3H), 7.61 (t, J = 8.0 Hz, 1H),
7.51-7.53 (mult, 2H), 6.47 (d, J = 15.7 Hz, 1H), 3.89 (s, 3H). (100
MHz, DMSO-d6) δ 166.6, 161.0, 158.1, 148.7, 148.3, 141.7, 137.2,
136.8, 135.7, 133.5, 133.2, 132.4, 130.5, 130.1, 130, 129.2, 124.4,
123.8, 122.9, 122.1, 121.6, 106.6, 55.8. HRMS calcd for
C24H17N3O6, 444.11964 [M þ H]þ; found, 444.11957 [M þ
H]þ. Anal. (C24H17N2O6) C, H, N. MP > 260 °C.
4-(6-Iodo-2-methyl-4-oxoquinazolin-3(4H)-yl)benzoic Acid (78).
Compound 78 was prepared via procedure B using compound 78a
(2.00 g, 7.00 mmol) and para-aminobenzoic acid (1.15 g, 8.40
mmol, 1.20 equiv). The crude material was recrystallized with ethyl
acetate and methanol to give an off-white solid (1.27 g, 45%). 1H
NMR (400 MHz, DMSO-d6) δ 13.27 (bs, 1H), 8.36 (d, J = 2.0 Hz,
1H), 8.15-8.11 (mult, 3H), 7.61 (d, J = 8.5 Hz, 2H), 7.47 (d, J =
8.5 Hz, 1H), 2.11 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ166.7,
160.0, 1547, 146.6, 143.0, 141.5, 134.5, 131.5, 130.7, 128.9, 122.3,
91.3, 24.2. HRMS calcd for C16H11IN2O3, 406.98934 [M þ H]þ;
found, 406.98893 [M þ H]þ.
(E)-4-(6-Iodo-2-(4-nitrostyryl)-4-oxoquinazolin-3(4H)-yl)benzoic
acid (72). Compound 72 was prepared via procedure C using
compound 72b (0.200 g, 0.490 mmol) and para-nitrobenzaldehyde
(0.099 g, 0.65 mmol, 1.3 equiv) to yield the title compound as a
1
yellow solid (0.174 g, 66%). H NMR (400 MHz, DMSO-d6) δ
8.32 (s, 1H), 8.16-8.12 (mult, 4H), 8.05 (s, 1H), 7.98 (d, J = 15.6
Hz, 1H), 7.77-7.68 (mult, 3H), 7.61-7.54(mult, 2H), 6.41(d, J =
15.6 Hz, 1H). 13C NMR (150 MHz, DMSO-d6) δ 166.6, 159.9,
151.4, 148.2, 146.4, 143.1, 137.0, 136.5, 136.4, 134.6, 133.3, 130.5,
130.1, 129.8, 129.3, 124.0, 122.5, 122.4, 122.1, 91.9. HRMS calcd
for C23H14IN3O5, 540.00574 [M þ H]þ; found, 540.00559 [M þ
H]þ. Anal. (C23H14IN3O5) C, H, N. MP > 260 °C.
(E)-3-(6-Iodo-2-(4-nitrostyryl)-4-oxoquinazolin-3(4H)-yl)benzoic
Acid (73). Compound 73 was prepared via procedure C using
compound 73b (0.800 g, 1.97 mmol) and para-nitrobenzaldehyde
(0.396 g, 2.62 mmol, 1.33 equiv) to yield the title compound as a
1
yellow solid (0.572 g, 54%). H NMR (400 MHz, DMSO-d6) δ
13.29 (bs, 1H), 8.32 (mult, 1H), 8.16-8.09 (mult, 5H), 7.94 (d, J =
15.3 Hz, 1H), 7.77 (s, 2H), 7.65-7.54 (mult, 3H), 6.47 (d, J = 15.3
Hz, 1H). 13C NMR (150 MHz, DMSO-d6) δ 166.8, 158.7, 151.6,
148.7, 147.2, 142.8, 136.7, 136.6, 135.9, 134.3, 133.2, 130.8, 130.6,
129.4, 128.9, 128.8, 123.9, 123.5, 123.4, 122.1, 92.2. HRMS calcd for
C23H14IN3O5, 540.00574 [M þ H]þ; found, 540.00548 [M þ H]þ.
Anal. (C23H14IN3O5) C, H, N. MP > 260 °C.
(E)-3-(6-Iodo-2-(3-nitrostyryl)-4-oxoquinazolin-3(4H)-yl)benzoic
Acid (74). Compound 74 was prepared via procedure C using
compound 73b (0.800 g, 1.97 mmol) and meta-nitrobenzaldehyde
(0.396 g, 2.62 mmol, 1.33 equiv) to yield the title compound as a
yellow solid (0.626 g, 59%). 1H NMR (400 MHz, DMSO-d6) δ8.32
(s, 1H), 8.16-8.12 (mult, 4H), 8.05 (s, 1H), 7.98 (d, J = 15.6 Hz,
1H), 7.77-7.68 (mult, 3H), 7.61-7.54 (mult, 2H), 6.41 (d, J = 15.6
Hz, 1H). 13C NMR (150 MHz, DMSO-d6) δ 166.6, 159.9, 151.4,
148.2, 146.4, 143.1, 137.0, 136.5, 136.4, 134.6, 133.3, 130.5, 130.1,
129.8, 129.3, 124.0, 122.5, 122.4, 122.1, 91.9. HRMS calcd for
C23H14IN3O5, 540.00574 [M þ H]þ; found, 540.00546 [M þ H]þ.
Anal. (C23H14IN3O5), C, H, N. MP > 260 °C.
(E)-4-(6-Methoxy-2-(4-nitrostyryl)-4-oxoquinazolin-3(4H)-yl)-
benzoic Acid (75). Compound 75 was prepared via procedure C
using compound 46b (0.730 g, 2.35 mmol) and para-nitrobenzal-
dehyde (0.473 g, 3.13 mmol, 1.3 equiv) to yield the title compound
as a yellow solid (0.559 g, 54%). 1H NMR (400 MHz, DMSO-d6)
δ 13.32 (bs, 1H), 8.17 (t, J = 8.8 Hz, 4H), 7.92 (d, J = 15.3, 1H),
7.78 (dd, J1 = 10 Hz, J2 = 4 Hz, 1H), 7.68 (d, J = 8.9 Hz, 1H),
7.63 (d, J = 8.2 Hz, 1H) 7.58-7.52 (mult, 2H), 6.51 (d, J = 15.7
Hz, 1H), 3.90 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 166.7,
158.4, 148.3, 147.4, 141.7, 141.3, 140.7, 135.7, 130.7, 129.4, 128.6,
124.5, 124.2, 106.6, 55.8. HRMS calcd for C24H17N2O6,
444.11964 [M þ H]þ; found, 444.11978 [M þ H]þ. Anal.
(C24H17N2O6) C, H, N. MP > 260 °C.
(E)-3-(6-Methoxy-2-(4-nitrostyryl)-4-oxoquinazolin-3(4H)-yl)-
benzoic Acid (76). Compound 76 was prepared via procedure C
using compound 76a (0.730 g, 2.35 mmol) and para-nitrobenzal-
dehyde (0.473 g, 3.13 mmol, 1.3 equiv) to yield the title compound
as a yellow solid (0.728 g, 70%). 1H NMR (400 MHz, DMSO-d6)
δ 13.34 (bs, 1H), 8.13-8.18 (mult, 3H), 8.04 (s, 1H), 7.91 (d, J =
15.7 Hz, 1H), 7.74-7.79 (mult, 3H), 7.65 (d, J = 9.0 Hz, 2H),
7.51-7.54 (mult, 2H), 6.50 (d, J = 15.7 Hz, 1H), 3.90 (s, 3H). 13C
NMR (100 MHz, DMSO-d6) δ 166.5, 161, 158.2, 148.6, 147.4,
141.7, 141.4, 137.1, 135.5, 133.4, 132.5, 130.1, 130, 129.2, 128.5,
124.4, 124.2, 124.2, 121.7, 106.6, 55.8. HRMS calcd for C24H17-
N3O6, 444.11964 [M þ H]þ; found, 444.11978 [M þ H]þ. Anal.
(C24H17N2O6) C, H, N. MP > 260 °C.
(E)-4-(6-Iodo-4-oxo-2-styrylquinazolin-3(4H)-yl)benzoic Acid (79).
Compound 79 was prepared via procedure C using compound 45b
(0.300 g, 0.740 mol) and benzaldehyde (0.100 mL, 0.980 mmol,
1.33 equiv). The crude material was purified by hot gravity
filtration of the title compound as a yellow solid after boiling in
methanol (0.070 g, 19%). 1H NMR (400 MHz, DMSO-d6) δ 8.40
(d, J = 1.9 Hz, 1H), 8.19-8.15 (mult, 3H), 7.92 (d, J = 15.5 Hz,
1H), 7.62-7.57 (mult, 3H), 7.39-7.35 (mult, 5H), 6.30 (d, J =
15.5 Hz, 1H). 13C NMR (150 MHz, DMSO-d6) δ 166.8, 160.0,
151.6, 146.7, 143.2, 140.4, 139.7, 134.6, 132.3, 130.7, 130.0,129.3,
129.2, 129.0, 127.7, 122.4, 119.5, 114.0, 91.5. HRMS calcd for
C23H15IN2O3, 495.02064; found, 495.01987 [M þ H]þ. Anal.
(C23H15IN2O3) C, H, N. MP > 260 °C.
4-(6-Methyl-4-oxo-2-phenethylquinazolin-3(4H)-yl)benzoic Acid
(81). Compound 80 (0.100 g, 0.26 mmol) was dissolved in DMF
(5.0 mL). Palladium on carbon (10%, 0.10 g, 10 wt %) was added.
A balloon filled with hydrogen was added, and the mixture was
stirred at room temperature for 1 h. The mixture was filtered over a
pad of Celite, and the resulting solution was concentrated in vacuo
to give a white solid. The solid was triturated with DCM and
obtained by filtration (0.016 g, 16%). 1H NMR (400 MHz, DMSO-
d6) δ 13.27 (bs, 1H), 8.09 (d, J = 8.2 Hz, 2H), 7.93 (s, 1H), 7.71 (d,
J = 8.6 Hz, 1H), 7.65 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 8.1 Hz, 2H),
7.22 (t, J = 7.4 Hz, 2H), 7.14 (t, J = 7.0 Hz, 1H), 7.06 (d, J = 7.0
Hz, 2H), 2.98 (t, J = 7.4 Hz, 2H), 2.58 (t, J = 7.4 Hz, 2H), 2.47 (s,
3H). 13C NMR (100 MHz, DMSO-d6) δ 166.7, 161.2, 154.6, 145.1,
141.3, 140.8, 136.4, 136.1, 131.5, 130.5, 129.2, 128.4, 128.2, 126.9,
126.1, 125.7, 120.2, 37.1, 32.0, 20.8. HRMS calcd for C24H20N2O3,
385.15534 [M þ H]þ; found, 385.15459 [M þ H]þ. Anal.
(C24H20N2O3) C: 72.02, H: 5.03, N: 7.19. MP > 260 °C
(E)-4-(6-Iodo-4-oxo-2-(2-(pyridin-3-yl)vinyl)quinazolin-3(4H)-
yl)benzoic Acid (98). Compound 98 was prepared via procedure
C using compound 72b (0.240 g, 0.591 mmol) and nicotinaldehyde
(0.084 g, 0.074 mL, 0.786 mmol, 1.33 equiv). The reaction mixture
was filtered and washed with MeOH to give the title compound as a
1
yellow solid (0.170 g, 58%). H NMR (400 MHz, DMSO-d6) δ
13.31 (bs, 1H), 8.67 (d, J = 2.4 Hz, 1H), 8.52 (dd, J1 = 4.7 Hz, J2 =
1.6Hz,1H),8.41(d,J= 2.0 Hz, 1H), 8.19 (dd, J1 =8.4Hz,J2 =8.4
Hz, 1H), 8.15 (d, J= 8.6 Hz, 2H), 7.93 (d, J=15.7Hz,1H),7.79(d,
J = 8.2 Hz, 1H), 7.58-7.63 (mult, 3H), 7.37 (dd, J1 = 8.0 Hz, J2 =
4.9 Hz, 1H), 6.43 (d, J = 15.7 Hz, 1H). 13C NMR (100 MHz,
DMSO-d6) δ 166.7, 159.9, 151.3, 149.5, 146.6, 143.3, 140.5, 136.3,
133.9, 131.7, 130.7, 130.5, 129.3, 124.1, 122.5, 121.6, 91.9. HRMS
calcd for C22H14IN3O3,494.00006 [M - H]þ; found, 494.00150
[M - H]þ. Anal. (C22H14IN3O3) C, H, N. MP > 260 °C.