The Journal of Organic Chemistry
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(d, J = 7.6 Hz, 2H), 7.53−7.57 (m, 5H), 8.01 (dd, J = 1.6, 8.4 Hz, 1H),
8.52 (dd, J = 2.8, 6,4 Hz, 1H), 8.55 (dd, J = 1.6, 4.0 Hz, 1H), 9.63 (br
s, 1H); 13C NMR (CDCl3, 100 MHz) 116.4, 121.5, 121.5, 127.3,
127.5, 127.5, 127.7, 128.8, 129.4, 129.5, 134.4, 136.1, 136.3, 138.4,
140.5, 140.7, 147.9, 167.6; IR (neat) 3350 w, 2311 w, 1672 m, 1575 w,
1517 s, 1480 m; MS m/z (relative intensity, %) 400 (M+, 27), 257
(100), 171 (1), 144 (2); HRMS calcd for C28H20N2O 400.1576, found
400.1573.
3-Fluoro-N-(quinolin-8-yl)-[1,1′-biphenyl]-2-carboxamide (2c): Rf
= 0.14 (hexane/EtOAc 8/1); white solid; yield 63 mg, 59%; mp 140
°C; 1H NMR (CDCl3, 400 MHz) 7.09−7.15 (m, 2H), 7.18−7.22 (m,
3H), 7.31 (dd, J = 8.0, 4.8 Hz, 1H), 7.39−7.46 (m, 5H), 8.04 (dd, J =
8.0, 1.6 Hz, 1H), 8.57 (dd, J = 4.0, 2.0 Hz, 1H), 8.71 (dd, J = 7.2, 2.0
Hz, 1H), 9.85 (br s, 1H); 13C NMR (CDCl3, 100 MHz) 115.0 (d, J =
22.0 Hz), 117.1, 121.7, 122.2, 125.1 (d, J = 17.3 Hz), 126.1, 127.5,
127.9, 128.0, 128.6, 128.7, 131.2, 134.2, 136.6, 138.2, 139.1, 142.5,
148.1, 159.9 (d, J = 250.2 Hz), 163.4; IR (neat) 3340 w, 3058 w, 2251
w, 1677 m, 1608 w, 1565 w, 1522 s, 1484 s; MS m/z (relative intensity,
%) 342 (M+, 37), 199 (100), 171 (27), 144 (9); HRMS calcd for
C22H15FN2O 342.1168, found 342.1165.
1H), 9.88(br s, 1H); 13C NMR (CDCl3, 100 MHz) 116.8, 121.5,
121.8, 127.3, 127.5, 127.8, 127.9, 128.0, 128.5, 129.06, 129.09, 129.2,
131.3, 134.4, 136.49, 136.47, 136.6, 138.2, 139.2, 139.7, 140.0, 140.6,
147.7, 168.0; HRMS calcd for C28H20N2O 400.1576, found 400.1573.
4-Chloro-N-(quinolin-8-yl)-[1,1′-biphenyl]-2-carboxamide (2i): Rf
= 0.29 (hexane/EtOAc 5/1); white solid; yield 77 mg, 68%; mp 150
°C; 1H NMR (CDCl3, 400 MHz) 7.17 (t, J = 7.2 Hz, 1H), 7.25−7.30
(m, 2H), 7.35 (dd, J = 8.4, 4.0 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H),
7.45−7.54 (m, 5H), 7.90 (d, J = 7.9 Hz, 1H), 8.07 (dd, J = 8.0, 1.6 Hz,
1H), 8.51 (dd, J = 4.0, 2.0 Hz, 1H), 8.77 (dd, J = 7.2, 1.2 Hz, 1H), 9.76
(br s, 1H); 13C NMR (CDCl3, 100 MHz) 116.5, 121.6, 121.9, 127.4,
127.8, 128.1, 128.7, 129.0, 129.4, 130.7, 132.2, 133.9, 134.3, 136.2,
137.5, 138.5, 138.8, 139.0, 148.0, 166.4; IR (neat) 3326 w, 2984 w,
2359 w, 1737 s, 1670 m, 1595 w, 1522 s, 1483 m; MS m/z (relative
intensity, %) 358 (M+, 49), 215 (100), 171 (11), 144 (23). HRMS
calcd for C22H15ClN2O 358.0873, found 358.0870.
4-Bromo-N-(quinolin-8-yl)-[1,1′-biphenyl]-2-carboxamide (2j): Rf
= 0.29 (hexane/EtOAc 5/1); white solid; yield 85 mg, 70%; mp 136
°C; 1H NMR (CDCl3, 400 MHz) 7.18 (t, J = 7.6 Hz, 1H), 7.26−7.30
(m, 2H), 7.34−7.36 (m, 2H), 7.45−7.53 (m, 4H), 7.68 (dd, J =8.4, 1.6
Hz, 1H), 8.06 (dd, J = 6.4, 1.2 Hz, 1H), 8.08 (d, J = 1.2 Hz, 1H), 8.52
(dd, J = 4.4, 1.6 Hz, 1H), 8.77 (dd, J = 7.6, 1.2 Hz, 1H), 9.75 (br s,
1H); 13C NMR (CDCl3, 100 MHz) 116.6, 121.6, 121.9, 121.9, 127.4,
127.8, 128.1, 128.7, 128.9, 132.2, 132.4, 133.6, 134.3, 136.2, 137.7,
138.0, 138.3, 139.0, 139.2, 139.6, 147.9, 166.3; IR (neat) 2984 w, 1738
s, 1676 w, 1525 w, 1483 w; MS m/z (relative intensity, %) 404 (57),
403 (42), 402 (M+, 58), 171 (18), 152 (100), 144 (40); HRMS calcd
for C22H15BrN2O 402.0368, found 402.0370.
4-Acetyl-N-(quinolin-8-yl)-[1,1′-biphenyl]-2-carboxamide (2k): Rf
= 0.08 (hexane/EtOAc 5/1). Colorless oil. yield 66 mg, 60%; 1H
NMR (CDCl3, 400 MHz) 2.71 (s, 3H), 7.21 (t, J = 8.0 Hz, 1H), 7.29−
7.37 (m, 3H), 7.47−7.55 (m, 4H), 7.60 (d, J = 7.6 Hz, 1H), 8.09 (d, J
= 8.0 Hz, 1H), 8.16 (dd, J = 7.6, 2.0 Hz, 1H), 8.49−8.52 (m, 2H), 8.80
(d, J = 7.6 Hz, 1H), 9.81 (br s, 1H); 13C NMR (CDCl3, 100 MHz)
27.0, 116.5, 121.6, 122.0, 127.4, 127.8, 128.5, 128.7, 129.0, 129.9,
130.0, 131.3, 134.4, 136.2, 136.3, 136.5, 138.4, 139.0, 144.8, 148.0,
167.0, 197.3; IR (neat) 3322 w, 3057 w, 2348 w, 1681 s, 1598 m, 1523
s, 1484 m; MS m/z (relative intensity, %) 366 (M+, 53), 223 (100),
171 (7), 144 (11); HRMS calcd for C24H18N2O2 366.1368, found
366.1369.
N-(Quinolin-8-yl)-4-(trifluoromethyl)-[1,1′-biphenyl]-2-carboxa-
mide (2l): Rf = 0.26 (hexane/EtOAc 5/1); white solid; yield 80 mg,
68%; 1H NMR (CDCl3, 400 MHz) 7.21 (t, J = 8.8 Hz, 1H), 7.29−7.36
(m, 3H), 7.46−7.54 (m, 4H), 7.61 (d, J = 8.4 Hz, 1H), 7.80 (dd, J =
8.0, 1.6 Hz, 1H), 8.07 (dd, J = 8.4, 1.6 Hz, 1H), 8.20 (s, 1H), 8.50 (dd,
J = 4.0, 2.0 Hz, 1H), 8.79 (dd, J = 8.0, 1.2 Hz, 1H), 9.78 (br s, 1H);
13C NMR (CDCl3, 100 MHz) 116.5, 121.6, 122.0, 124.0 (q, J = 272.2
N-(Quinolin-8-yl)-3-(trifluoromethyl)-[1,1′-biphenyl]-2-carboxa-
mide (2d): Rf = 0.20 (hexane/EtOAc 5/1); white solid; yield 75 mg,
1
63%; mp 143 °C; H NMR (CDCl3, 400 MHz) 7.13 (t, J = 7.2 Hz,
1H), 7.21−7.26 (m, 2H), 7.37 (dd, J = 8.4, 4.0 Hz, 1H), 7.46−7.51
(m, 4H), 7.61−7.67 (m, 2H), 7.79 (dd, J = 7.2, 2.0 Hz, 1H), 8.09 (dd,
J = 8.0, 2.0 Hz, 1H), 8.63 (dd, J = 4.0, 2.0 Hz, 1H), 8.69 (dd, J = 6.4,
2.4 Hz, 1H), 9.74 (br s, 1H); 13C NMR (CDCl3, 100 MHz) 116.8,
121.6, 122.1, 123.9 (q, J = 274.0 Hz), 125.5 (q, J = 4.8 Hz), 127.4,
127.9, 128.1, 128.2 (q, J = 31.6 Hz), 128.4, 128.4, 128.8, 129.6, 134.1,
135.0, 136.3, 138.4, 139.0, 141.5, 148.2, 165.3; IR (neat) 3338 w, 3059
w, 2251 w, 1679 m, 1596 w, 1580 w, 1522 s, 1484 m; MS m/z (relative
intensity, %) 392 (M+, 49) 249 (100), 171 (8.8), 144 (8); HRMS
calcd for C23H15F3N2O 392.1136, found 392.1133
4-(Dimethylamino)-N-(quinolin-8-yl)-[1,1′-biphenyl]-2-carboxa-
mide (2e): Rf = 0.20 (hexane/EtOAc 5/1); pale yellow solid; yield 61
1
mg, 53%; H NMR (CDCl3, 400 MHz) 3.05 (s, 6H), 6.91 (m, 1H),
7.07 (t, J = 7.6 Hz, 1H), 7.20−7.25 (m, 3H), 7.31 (dd, J = 8.4, 4.0 Hz,
1H), 7.37 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.47−7.53 (m,
3H), 8.04 (dd, J = 8.4, 1.2 Hz, 1H), 8.47 (dd, J = 4.0, 1.6 Hz, 1H), 8.83
(d, J = 7.2 Hz, 1H), 9.76 (br s, 1H); 13C NMR (CDCl3, 100 MHz)
40.7, 113.0, 114.6, 116.3, 121.5, 126.8, 127.4, 127.8, 128.1, 128.3,
129.1, 131.7, 134.8, 136.0, 136.8, 138.6, 140.3, 147.8, 149.9, 168.8;
HRMS calcd for C24H21N3O 367.1685, found 367.1687.
4-Methoxy-N-(quinolin-8-yl)-[1,1′-biphenyl]-2-carboxamide (2f):
Rf = 0.17 (hexane/EtOAc 5/1); white solid; yield 75 mg, 66%; mp 144
1
°C; H NMR (CDCl3, 400 MHz) 3.90 (s, 3H), 7.08−7.13 (m, 2H),
7.23−7.26 (m, 2H), 7.38−7.52 (m, 6H), 7.31 (dd, J = 8.4, 4.0 Hz,
1H), 8.04 (d, J = 8.4 Hz, 1H), 8.48 (dd, J =4.0, 1.6 Hz, 1H), 8.81 (d, J
= 7.6 Hz, 1H), 9.78 (br s, 1H); 13C NMR (CDCl3, 100 MHz) 55.7,
113.8, 116.4, 117.1, 121.5, 121.7, 127.3, 127.8, 128.4, 129.1, 132.1,
132.8, 134.5, 136.1, 137.0, 138.4, 139.8, 147.8, 159.1, 167.7; IR (neat)
3325 w, 2359 w, 2251 w, 1662 w, 1604 w, 1524 m, 1482 w; MS m/z
(relative intensity, %) 354 (M+, 32), 211 (100), 171 (3), 144 (8).
HRMS calcd for C23H18N2O2 354.1368, found 354.1371.
Hz), 126.7, 127.2, 127.3, 127.8, 128.5, 128.8, 129.0, 130.1 (q, J = 32.7
Hz), 131.4, 134.2, 136.2, 136.7, 138.4, 138.7, 143.7, 148.0, 166.4;
HRMS calcd for C23H15F3N2O 392.1136, found 392.1134.
4,5-Dimethoxy-N-(quinolin-8-yl)-[1,1′-biphenyl]-2-carboxamide
(10): Rf = 0.09 (hexane/EtOAc 5/1); white solid; yield 79 mg, 65%;
1H NMR (CDCl3, 400 MHz) 3.97 (s, 3H), 4.01 (s, 3H), 6.92 (s, 1H),
7.15 (t, J = 7.2 Hz, 1H), 7.26−7.33 (m, 3H), 7.43 (d, J = 8.4 Hz, 1H),
7.49−7.54 (m, 4 H), 8.04 (d, J = 8.4 Hz, 1H), 8.43 (d, J = 4.4 Hz, 1H),
8.82 (d, J = 7.6 Hz, 1H), 9.69 (br s, 1H); 13C NMR (CDCl3, 100
MHz) 56.17, 56.22, 112.6, 113.3, 116.1, 121.4, 127.3, 127.6, 127.7,
128.0, 128.3, 128.5, 129.4, 133.8, 134.7, 135.9, 138.4, 140.0, 147.6,
148.4, 150.6, 167.3; HRMS calcd for C24H20N2O3 384.1474, found
384.1469.
5-Fuoro-3-methyl-N-(quinolin-8-yl)-[1,1′-biphenyl]-2-carboxa-
mide (12): Rf = 0.31 (hexane/EtOAc 5/1); colorless oil; yield 103 mg,
96%; 1H NMR (CDCl3, 400 MHz) 2.53 (s, 3H), 6.99−7.02 (m, 2H),
7.09 (t, J = 7.2 Hz, 1H), 7.22 (dd, J = 15.2, 18.0 Hz, 2H), 7.35 (dd, J =
8.4, 4.0 Hz, 1H), 7.44−7.51 (m, 4H), 8.06 (dd, J = 8.0, 1.6 Hz, 1H),
8.60 (dd, J = 4.4, 1.2 Hz, 1H), 8.75 (dd, J = 7.2, 1.2 Hz, 1H), 9.61 (br
s,1H); 13C NMR (CDCl3, 100 MHz) 20.1, 114.4 (d, J = 22.0 Hz),
116.2, 116.4, 116.6, 121.8 (d, J = 32.6 Hz), 127.4, 127.9, 128.5 (d, J =
13.4 Hz), 131.8 (d, J = 151.4 Hz), 133.2, 134.3, 136.3, 138.3, 139.1 (d,
4-Methyl-N-(quinolin-8-yl)-[1,1′-biphenyl]-2-carboxamide (2g):
1
Rf = 0.29 (hexane/EtOAc 5/1); white solid; yield 72 mg, 69%; H
NMR (CDCl3, 400 MHz) 2.47 (s, 3H), 7.14 (t, J = 7.6 Hz, 1H), 7.24−
7.28 (m, 2H), 7.34(dd, J = 8.4, 4.0, 1H), 7.38−7.39 (m, 2H), 7.43−
7.53 (m, 4H), 7.72 (s, 1H), 8.06 (dd, J = 8.4, 1.6 Hz, 1H), 8.51 (dd, J
= 4.0, 1.2 Hz, 1H), 8.81 (dd, J = 7.2, 1.6 Hz,1H), 9.75 (br s, 1H); 13C
NMR (CDCl3, 100 MHz) 21.2, 116.3, 121.5, 121.5, 127.4, 127.5,
127.8, 128.4, 129.1 129.9, 130.7, 131.4, 134.7, 136.0, 137.5, 137.6,
138.5, 140.1, 147.8, 168.1; HRMS calcd for C23H18N2O 338.1419,
found 338.1420.
N-(Quinolin-8-yl)-[1,1′:4′,1″-terphenyl]-2′-carboxamide (2h): Rf =
1
0.40 (hexane/EtOAc 5/1); white solid; yield 79 mg, 65% H NMR
(CDCl3, 400 MHz) 7.18 (t, J = 7.6 Hz, 1H), 7.28−7.32 (m, 2H),
7.35−7.42 (m, 2H), 7.47−7.59 (m, 7H), 7.72 (dd, J = 3.2, 1.6 Hz,
2H), 7.80 (dd, J = 8.0, 2.0 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.15 (d, J
= 1.6 Hz, 1H), 8.53 (dd, J = 4.0, 2.0 Hz, 1H), 8.83 (dd, J = 7.6, 1.2 Hz,
G
dx.doi.org/10.1021/jo501697n | J. Org. Chem. XXXX, XXX, XXX−XXX