10.1002/ejoc.201701772
European Journal of Organic Chemistry
FULL PAPER
Hz, 1H), 7.48 – 7.43 (m, 2H), 7.38 (dd, J = 0.7, 2.1 Hz, 1H), 7.34
– 7.31 (m, 1H), 7.29 (dd, J = 1.4, 2.9 Hz, 1H), 7.18 – 7.14 (m, 2H),
7.04 (dt, J = 1.1, 5.1 Hz, 1H), 3.94 (s, 3H), 3.67 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 160.5, 153.9, 144.5, 141.2, 132.9, 132.0,
130.9, 129.9, 129.7, 127.8, 126.6, 125.9, 125.7, 123.0, 120.9,
117.1, 115.5, 115.3, 55.8, 27.9; HRMS (ESI, [M+H]+) calcd for
C22H18N3O2S 388.1114, found 388.1106.
general procedure A as an off-white solid (20.0 mg, 52%): Rf =
0.38 (20:1 DCM:MeOH); 1H NMR (400 MHz, CDCl3) δ 8.81 (d, J
= 1.4 Hz, 1H), 8.63 (s, 1H), 8.60 – 8.55 (m, 1H), 8.22 (dt, J = 0.7,
8.9 Hz, 1H), 7.79 (ddd, J = 1.0, 1.8, 8.4 Hz, 1H), 7.70 (ddd, J =
1.7, 2.4, 7.9 Hz, 1H), 7.63 – 7.55 (m, 3H), 7.50 – 7.46 (m, 1H),
7.42 – 7.39 (m, 1H), 7.33 (ddd, J = 0.8, 4.8, 7.8 Hz, 1H), 3.68 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 153.5, 149.1, 148.2, 144.9,
136.4, 135.7, 135.7, 135.6, 134.3, 132.9, 131.7, 131.1, 130.2,
129.1, 129.0, 126.8, 126.4, 123.8, 123.5, 118.6, 115.4, 28.1;
HRMS (ESI, [M+H]+) calcd for C22H16ClN4O 387.1007, found
387.1000.
1-(3-Methoxyphenyl)-3-methyl-8-(pyridin-3-yl)-1,3-dihydro-
2H-imidazo[4,5-c]quinolin-2-one (5j). Prepared by following the
general procedure A as an off-white solid (19.5 mg, 51%): Rf =
0.42 (20:1 DCM:MeOH); 1H NMR (400 MHz, DMSO-d6) δ 9.02 (s,
1H), 8.54 (dt, J = 1.5, 3.9 Hz, 2H), 8.13 (dd, J = 0.6, 8.9 Hz, 1H),
7.93 (dd, J = 2.1, 8.9 Hz, 1H), 7.80 (ddd, J = 1.6, 2.4, 7.9 Hz, 1H),
7.62 (ddd, J = 0.6, 7.7, 8.2 Hz, 1H), 7.45 (ddd, J = 0.9, 4.8, 8.0
Hz, 1H), 7.31 – 7.23 (m, 4H), 3.81 (s, 3H), 3.61 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ 160.8, 153.3, 149.3, 147.7, 144.4, 136.9,
135.1, 134.4, 134.3, 134.2, 131.5, 131.2, 129.2, 125.9, 124.4,
123.7, 121.4, 118.4, 115.9, 115.2, 115.1, 56.1, 28.1; HRMS (ESI,
[M+H]+) calcd for C23H19N4O2 383.1503, found 383.1513.
3-Methyl-8-(pyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)-1,3-
dihydro-2H-imidazo[4,5-c]quinolin-2-one (5o). Prepared by
following the general procedure B as an off-white solid (26.9 mg,
64%): Rf = 0.33 (20:1 DCM:MeOH); 1H NMR (400 MHz, CDCl3) δ
8.84 (s, 1H), 8.61 – 8.54 (m, 2H), 8.24 (dd, J = 0.6, 8.8 Hz, 1H),
7.92 – 7.86 (m, 2H), 7.83 – 7.77 (m, 3H), 7.62 (ddd, J = 1.7, 2.4,
7.9 Hz, 1H), 7.33 – 7.28 (m, 2H), 3.70 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 153.5, 149.2, 148.2, 144.9, 136.0, 135.9, 135.6, 134.3,
133.0, 132.9, 132.6, 132.2, 131.9, 130.9, 128.9, 126.7, 126.5,
125.6, 123.8, 123.6, 118.4, 115.4, 28.1; HRMS (ESI, [M+H]+)
calcd for C23H16F3N4O 421.1271, found 421.1281.
1-(3-Hydroxyphenyl)-3-methyl-8-(pyridin-3-yl)-1,3-dihydro-
2H-imidazo[4,5-c]quinolin-2-one (5k). Prepared by following
the general procedure A as a yellow solid (21.6 mg, 59%): Rf =
0.37 (20:1 DCM:MeOH); 1H NMR (400 MHz, CDCl3) δ 8.79 (d, J
= 1.0 Hz, 1H), 8.57 (d, J = 2.5 Hz, 1H), 8.51 (dd, J = 1.6, 4.9 Hz,
1H), 8.18 (dd, J = 1.0, 8.9 Hz, 1H), 7.82 (ddd, J = 1.5, 2.4, 8.0 Hz,
1H), 7.75 (dd, J = 2.2, 8.9 Hz, 1H), 7.52 (d, J = 2.1 Hz, 1H), 7.43
(t, J = 8.0 Hz, 1H), 7.38 – 7.34 (m, 1H), 7.09 – 7.00 (m, 3H), 3.67
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.3, 153.9, 148.1, 147.4,
144.9, 136.0, 134.9, 134.7, 132.9, 131.4, 131.0, 129.9, 126.0,
8-(6-Aminopyridin-3-yl)-3-methyl-1-(3-
(trifluoromethyl)phenyl)-1,3-dihydro-2H-imidazo[4,5-
c]quinolin-2-one (5p). Prepared by following the general
procedure B as an off-white solid (26.5 mg, 61%): Rf = 0.33 (20:1
DCM:MeOH); 1H NMR (400 MHz, DMSO-d6) δ 8.92 (s, 1H), 8.19
– 8.15 (m, 1H), 8.08 – 7.98 (m, 3H), 7.96 – 7.90 (m, 1H), 7.86 (dd,
J = 0.8, 2.6 Hz, 1H), 7.78 (dd, J = 2.1, 8.9 Hz, 1H), 7.33 (dd, J =
124.2, 123.3, 119.5, 119.1, 117.8, 116.4, 115.5, 28.1; HRMS (ESI, 2.6, 8.7 Hz, 1H), 6.98 – 6.93 (m, 1H), 6.41 (dd, J = 0.8, 8.7 Hz,
[M+H]+) calcd for C22H17N4O2 369.1346, found 369.1358.
1H), 6.17 (s, 2H), 3.56 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ
159.9, 153.4, 146.0, 143.8, 136.9, 135.8, 135.3, 133.9, 133.4,
131.7, 131.3, 130.9, 128.4, 126.7, 126.5, 125.4, 123.7, 123.1,
122.8, 115.3, 115.1, 108.4, 28.1; HRMS (ESI, [M+Na]+) calcd for
C23H16F3N5NaO 458.1199, found 458.1220.
3-(1-(2-Hydroxyphenyl)-3-methyl-2-oxo-2,3-dihydro-1H-
imidazo[4,5-c]quinolin-8-yl)benzonitrile (5l). Prepared by
following the general procedure A as a tan solid (13.2 mg, 34%):
Rf = 0.46 (20:1 DCM:MeOH); 1H NMR (400 MHz, DMSO-d6) δ
10.17 (s, 1H), 8.99 (s, 1H), 8.10 (dd, J = 0.6, 8.9 Hz, 1H), 7.95
(dd, J = 2.2, 8.9 Hz, 1H), 7.81 (dt, J = 1.3, 7.6 Hz, 1H), 7.73 (td, J
= 0.7, 1.9 Hz, 1H), 7.70 (ddd, J = 1.2, 2.0, 7.9 Hz, 1H), 7.62 (td, J
= 0.7, 7.9 Hz, 1H), 7.55 – 7.48 (m, 2H), 7.33 (dd, J = 0.7, 2.2 Hz,
1H), 7.21 – 7.16 (m, 1H), 7.09 (td, J = 1.4, 7.6 Hz, 1H), 3.61 (s,
3H); 13C NMR (100 MHz, DMSO-d6) δ 154.6, 152.9, 143.8, 140.2,
134.6, 133.8, 131.3, 131.1, 130.9, 130.7, 130.7, 130.3, 129.8,
129.2, 125.1, 123.3, 122.4, 119.9, 118.4, 117.7, 116.8, 115.1,
112.3, 27.6; HRMS (ESI, [M+H]+) calcd for C24H17N4O2 393.1346,
found 393.1351.
8-(6-Hydroxypyridin-3-yl)-3-methyl-1-(3-
(trifluoromethyl)phenyl)-1,3-dihydro-2H-imidazo[4,5-
c]quinolin-2-one (5q). Prepared by following the general
procedure B as an off-white solid (23.9 mg, 55%): Rf = 0.23 (20:1
DCM:MeOH); 1H NMR (400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.17
(d, J = 2.2 Hz, 1H), 8.09 – 8.01 (m, 3H), 7.96 (d, J = 7.8 Hz, 1H),
7.81 (dd, J = 2.2, 9.0 Hz, 1H), 7.50 (d, J = 2.8 Hz, 1H), 7.26 (dd,
J = 2.8, 9.6 Hz, 1H), 6.92 (d, J = 2.1 Hz, 1H), 6.32 (d, J = 9.6 Hz,
1H), 3.60 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 161.5, 152.9,
143.4, 138.7, 136.3, 133.5, 133.4, 133.2, 131.2, 130.9, 130.7,
130.4, 128.0, 126.3, 126.0, 126.0, 125.0, 124.6, 123.4, 122.2,
115.0, 114.7, 27.7; HRMS (ESI, [M+H]+) calcd for C23H16F3N4O2
437.1220, found 437.1217.
1-(4-Fluorophenyl)-8-(furan-3-yl)-3-methyl-1,3-dihydro-2H-
imidazo[4,5-c]quinolin-2-one (5m). Prepared by following the
general procedure A as a yellow solid (24.0 mg, 67%): Rf = 0.80
(20:1 DCM:MeOH); 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H),
8.09 (dd, J = 0.6, 8.9 Hz, 1H), 7.68 (dd, J = 2.0, 8.9 Hz, 1H), 7.59
(dd, J = 0.9, 1.6 Hz, 1H), 7.57 – 7.52 (m, 2H), 7.44 (t, J = 1.7 Hz,
1H), 7.39 – 7.34 (m, 2H), 7.20 (dd, J = 0.6, 2.0 Hz, 1H), 6.28 (dd,
J = 0.9, 1.9 Hz, 1H), 3.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
164.5, 153.8, 144.7, 144.3, 139.2, 132.1, 131.6, 131.3, 130.9,
130.8, 130.3, 129.1, 125.8, 125.6, 123.3, 117.3, 117.0, 116.2,
115.6, 108.2, 28.0; HRMS (ESI, [M+H]+) calcd for C21H15FN3O2
360.1143, found 360.1136.
3-(3-Methyl-2-oxo-1-(4-(trifluoromethyl)phenyl)-2,3-dihydro-
1H-imidazo[4,5-c]quinolin-8-yl)benzonitrile (5r). Prepared by
following the general procedure B as a white solid (22.1 mg, 50%):
1
Rf = 0.58 (20:1 DCM:MeOH); H NMR (400 MHz, CDCl3) δ 8.85
(d, J = 1.1 Hz, 1H), 8.23 (dd, J = 1.1, 8.9 Hz, 1H), 7.98 – 7.94 (m,
2H), 7.81 – 7.77 (m, 1H), 7.73 (dt, J = 1.0, 8.8 Hz, 2H), 7.67 –
7.65 (m, 1H), 7.61 (s, 1H), 7.48 – 7.42 (m, 2H), 7.23 (d, J = 2.1
Hz, 1H), 3.71 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 153.4, 145.1,
141.2, 138.7, 136.6, 133.2, 132.1, 132.0, 131.5, 131.0, 130.5,
130.0, 129.3, 129.0, 127.3, 127.3, 127.3, 126.1, 123.7, 118.6,
118.4, 115.3, 113.6, 28.2; HRMS (ESI, [M+H]+) calcd for
C25H16F3N4O 445.1271, found 445.1280.
1-(3-Chlorophenyl)-3-methyl-8-(pyridin-3-yl)-1,3-dihydro-2H-
imidazo[4,5-c]quinolin-2-one (5n). Prepared by following the
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