4.5.1.5. N-(4-fluorophenyl)-N-(4-((5-methoxy-2,3-dihydro-[1,4]-
dioxino[2,3-f]quinazolin-10-yl)oxy)phenyl)cyclopropane-1,1-dic-
arboxamide (7a)
137.38, 132.96, 129.19, 126.50, 125.96, 123.81, 122.57, 121.70,
121.17, 102.82, 100.54, 64.82, 63.95, 56.61, 40.65, 40.44, 40.24,
40.03, 39.82, 39.61, 39.40, 31.48, 16.70. HRMS (ESI) m/z calcd
for C29H24F3N4O6+ [M+H]+, 581.1642; found, 581.1606
white solid; yield: 85%; mp: 242-243 ºC. 1H NMR (400 MHz,
DMSO-d6, δ ppm): 8.41 (s, 1H), 7.71 – 7.57 (m, 4H), 7.20 – 7.06
(m, 4H), 4.44 (d, J = 3.0 Hz, 2H), 4.38 (d, J = 2.8 Hz, 2H), 3.96
(s, 3H), 1.43 (s, 4H). 13C NMR (101 MHz, DMSO-d6, δ ppm):
168.77, 168.62, 165.36, 159.11, 156.73, 155.07, 152.30, 148.18,
147.87, 147.85, 147.84, 138.54, 132.50, 122.41, 122.34, 122.06,
121.59, 115.04, 114.82, 102.35, 100.08, 64.38, 63.49, 56.18,
40.15, 39.94, 39.73, 39.52, 39.31, 39.10, 38.89, 30.92, 15.86.
HRMS (ESI) m/z calcd for C28H24FN4O6 [M+H]+, 531.1674;
found, 531.1664.
4.5.1.10. N-(4-isopropylphenyl)-N-(4-((5-methoxy-2,3-dihydro-
[1,4]dioxino[2,3-f]quinazolin-10-yl)oxy)phenyl)cyclopropane-1,1-
dicarboxamide (7f)
white solid; yield: 75%; mp: 235-238 ºC. 1H NMR (400 MHz,
DMSO-d6, δ ppm): 10.11 (s, 2H), 8.41 (s, 1H), 7.69 (d, J = 8.9
Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 7.17 (dd, J = 8.8, 2.9 Hz, 4H),
7.02 (s, 1H), 4.48 – 4.42 (m, 2H), 4.38 (d, J = 2.8 Hz, 2H), 3.96
(s, 3H), 1.49 (d, J = 1.2 Hz, 4H), 1.18 (d, J = 6.9 Hz, 6H).13C
NMR (101 MHz, DMSO-d6, δ ppm): 168.45, 168.13, 165.31,
155.07, 152.27, 148.30, 148.19, 143.75, 138.50, 136.57, 136.12,
132.49, 126.21, 122.16, 121.70, 120.63, 102.31, 100.08, 64.37,
63.48, 56.17, 32.91, 31.22, 23.98, 15.62. HRMS (ESI) m/z calcd
4.5.1.6. N-(4-((5-methoxy-2,3-dihydro-[1,4]dioxino[2,3-f]quinaz-
olin-10-yl)oxy)phenyl)-N-phenylcyclopropane-1,1-dicarboxamide
(7b)
1
white solid; yield: 78%; mp: 237-239ºC. H NMR (400 MHz,
+
for C31H31N4O6 [M+H]+, 555.2238; found, 555.2230.
DMSO-d6, δ ppm): 8.41 (s, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.62 (d,
J = 7.8 Hz, 2H), 7.28 (t, J = 7.8 Hz, 2H), 7.12 (d, J = 8.8 Hz,
2H), 7.02 (d, J = 9.8 Hz, 2H), 4.44 (d, J = 2.2 Hz, 2H), 4.38 (s,
2H), 3.95 (s, 3H), 1.43 (d, J = 4.0 Hz, 4H). 13C NMR (101 MHz,
DMSO-d6, δ ppm): 169.07, 165.39, 155.05, 152.31, 148.17,
147.60, 138.55, 132.48, 128.49, 122.86, 121.97, 121.82, 120.47,
102.37, 100.06, 64.37, 63.50, 56.16, 30.70, 16.08. HRMS (ESI)
m/z calcd for C28H25N4O6+ [M+H]+, 513.1769; found, 513.1756.
4.5.1.11. N-(4-((5-methoxy-2,3-dihydro-[1,4]dioxino[2,3-f]quin
-azolin-10-yl)oxy)phenyl)-N-(4-methoxyphenyl)cyclopropane-1,
1-dicarboxamide (7g)
white solid; yield: 63%; mp: 210-212 ºC. 1H NMR (400 MHz,
DMSO-d6, δ ppm): 10.23 (s, 1H), 9.96 (s, 1H), 8.41 (s, 1H), 7.69
(d, J = 8.9 Hz, 2H), 7.56 – 7.49 (m, 2H), 7.21 – 7.13 (m, 2H),
7.03 (s, 1H), 6.92 – 6.84 (m, 2H), 4.45 (dd, J = 5.3, 2.3 Hz, 2H),
4.41 – 4.36 (m, 2H), 3.96 (s, 3H), 3.73 (s, 3H), 1.49 (s, 4H). 13C
NMR (101 MHz, DMSO-d6, δ ppm): 168.89, 168.61, 165.76,
156.06, 155.54, 152.73, 148.74, 148.66, 138.98, 136.58, 132.97,
132.27, 122.77, 122.59, 122.08, 114.09, 102.79, 100.55, 64.83,
63.95, 56.64, 55.65, 40.64, 40.43, 40.22, 40.01, 39.81, 39.60,
4.5.1.7. N-(4-chlorophenyl)-N-(4-((5-methoxy-2,3-dihydro-[1,4]
dioxino[2,3-f]quinazolin-10-yl)oxy)phenyl)cyclopropane-1,1-dic-
arboxamide (7c)
1
white solid; yield: 71%; mp:249-251 ºC. H NMR (400 MHz,
DMSO-d6, δ ppm): 8.42 (s, 1H), 7.65 (dd, J = 11.0, 9.0 Hz, 4H),
7.26 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 8.7 Hz, 2H), 7.04 (s, 1H),
4.45 (d, J = 2.9 Hz, 2H), 4.39 (d, J = 2.4 Hz, 2H), 3.96 (s, 3H),
1.35 (s, 4H). 13C NMR (101 MHz, DMSO-d6, δ ppm): 169.27,
169.25, 165.38, 155.06, 152.32, 148.17, 147.55, 147.52, 138.55,
132.48, 128.16, 122.36, 122.05, 121.29, 102.35, 100.07, 64.36,
63.48, 56.17, 30.65, 16.20. HRMS (ESI) m/z calcd for
+
39.39, 31.52, 16.05. HRMS (ESI) m/z calcd for C29H27N4O7 ,
[M+H]+, 543.1874; found, 543.1871.
4.5.1.12. N-(3-chloro-4-fluorophenyl)-N-(4-((5-methoxy-2,3-dih
-ydro-[1,4]dioxino[2,3-f]quinazolin-10-yl)oxy)phenyl)cyclopro-
pane-1,1-dicarboxamide (7h)
+
C28H24ClN4O6 [M+H]+, 547.1379; found, 547.1376
white solid; yield: 69%; mp: 235-238 ºC. 1H NMR (400 MHz,
DMSO-d6, δ ppm): 10.22 (d, J = 43.1 Hz, 2H), 8.41 (s, 1H), 7.98
(dd, J = 6.9, 2.3 Hz, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.57 (d, J =
7.5 Hz, 1H), 7.36 (t, J = 9.0 Hz, 1H), 7.15 (d, J = 8.9 Hz, 2H),
7.04 (s, 1H), 4.45 (d, J = 2.4 Hz, 2H), 4.38 (d, J = 1.9 Hz, 2H),
3.96 (s, 3H), 1.48 (s, 4H). 13C NMR (101 MHz, DMSO-d6, δ
ppm): 168.50, 168.21, 165.04, 155.18, 152.70, 152.33, 148.26,
140.29, 138.53, 132.58, 129.41, 122.09, 120.87, 120.80, 118.91,
118.73, 117.24, 117.07, 116.67, 116.46, 113.99, 102.36, 100.08,
64.40, 63.53, 56.21, 31.85, 15.53. HRMS (ESI) m/z calcd for
4.5.1.8. N-(4-((5-methoxy-2,3-dihydro-[1,4]dioxino[2,3-f]quinaz
olin-10-yl)oxy)phenyl)-N-(p-tolyl)cyclopropane-1,1-dicarboxami-
de (7d)
white solid; yield: 73%; mp: 237-239 ºC. 1H NMR (400 MHz,
DMSO-d6, δ ppm): 10.11 (s, 2H), 8.40 (s, 1H), 7.68 (d, J = 8.4
Hz, 2H), 7.50 (d, J = 7.9 Hz, 2H), 7.13 (dd, J = 19.7, 8.1 Hz, 4H),
7.02 (s, 1H), 4.41 (d, J = 23.7 Hz, 4H), 3.95 (s, 3H), 2.25 (s, 3H),
1.50 (s, 4H). 13C NMR (101 MHz, DMSO-d6, δ ppm): 168.54,
168.21, 165.27, 155.08, 152.24, 148.34, 148.18, 138.51, 136.21,
136.03, 132.62, 132.50, 128.88, 122.10, 121.74, 120.60, 102.32,
100.06, 64.36, 63.48, 56.16, 40.15, 31.15, 20.43, 15.63. HRMS
+
C28H23ClFN4O6 [M+H]+, 565.1285; found, 565.1281.
+
4.5.1.13. N-(3-fluoro-4-((5-methoxy-2,3-dihydro-[1,4]dioxino[2,3-
f]quinazolin-10-yl)oxy)phenyl)-N-(3-fluorophenyl)cyclopropane
-1,1-dicarboxamide (7i)
(ESI) m/z calcd for C29H27N4O6 [M+H]+, 527.1925; found,
527.1929.
4.5.1.9. N-(4-((5-methoxy-2,3-dihydro-[1,4]dioxino[2,3-f]quina
zolin-10-yl)oxy)phenyl)-N-(4-(trifluoromethyl)phenyl)cyclopro-
pane-1,1-dicarboxamide (7e)
white solid; yield: 73%; mp: 231-237 ºC. 1H NMR (400 MHz,
DMSO-d6, δ ppm): 1H NMR (400 MHz, DMSO) δ 10.32 (s, 2H),
8.41 (s, 1H), 7.75 – 7.58 (m, 3H), 7.45 – 7.27 (m, 2H), 7.16 (d, J
= 8.9 Hz, 2H), 7.03 (s, 1H), 6.88 (td, J = 8.3, 1.9 Hz, 1H), 4.48 –
4.42 (m, 2H), 4.38 (d, J = 2.8 Hz, 2H), 3.96 (s, 3H), 1.48 (d, J =
3.7 Hz, 4H). 13C NMR (101 MHz, DMSO-d6, δ ppm): 169.01,
168.73, 165.76, 163.70, 161.30, 155.54, 152.73, 148.73, 148.65,
138.98, 136.71, 132.96, 130.52, 130.42, 122.57, 122.16, 116.53,
115.33, 110.30, 110.09, 107.72, 107.46, 102.79, 100.55, 64.83,
white solid; yield: 74%; mp: 210-213 ºC. 1H NMR (400 MHz,
DMSO-d6, δ ppm): 8.41 (s, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.72 –
7.66 (m, 2H), 7.59 (d, J = 8.5 Hz, 2H), 7.19 – 7.12 (m, 2H), 7.02
(s, 1H), 4.45 (d, J = 3.1 Hz, 2H), 4.39 (d, J = 2.9 Hz, 2H), 3.96 (s,
3H), 1.43 (s, 4H). 13C NMR (101 MHz, DMSO-d6, δ ppm):
170.02, 169.53, 165.78, 155.52, 152.73, 148.66, 148.35, 139.00,