Y. Fang, R.C. Larock / Tetrahedron 68 (2012) 2819e2826
2825
(300 MHz, CDCl3)
d
8.16 (d, J¼4.2 Hz, 1H), 7.46 (d, J¼7.5 Hz, 1H), 7.40
142.6, 137.0, 131.7, 129.7, 129.4, 125.6, 121.5, 119.1, 118.5, 117.34,
117.32, 46.0; LRMS (EI) 314 (M); HRMS (EI) calcd for C15H11BrN2O
(M) 314.0055, found 314.0053; IR (KBr, cmꢁ1) 3084 (w), 2954 (m),
2924 (m), 2870 (w), 1639 (m), 1587 (s).
(t, J¼7.2 Hz, 1H), 7.32 (d, J¼7.5 Hz, 1H), 7.20 (m, 2H), 6.66 (t,
J¼6.0 Hz, 1H), 6.45 (d, J¼8.4 Hz, 1H), 6.30 (s, 1H), 1.41 (s, 9H); 13C
NMR (75 MHz, CDCl3) d 158.3, 148.7, 145.9, 138.8, 137.8, 128.8, 127.4,
127.3, 126.1, 114.3, 107.2, 35.2, 30.8; LRMS (EI) 226 (M); HRMS (EI)
calcd for C15H18N2 (M) 226.1470, found 226.1475.
4.4.3. 7-Iodo-10-methylbenzo[b][1,8]naphthyridin-5(10H)-one
(5ac). Yellow solid: mp 198e199 ꢀC; Rf¼0.13 (8:1 petroleum ether/
4.3.8. N-[2-(Cyclohex-1-en-1-yl)ethyl]pyridin-2-amine
EtOAcþ1% TEA); 1H NMR (400 MHz, CDCl3)
d 8.78 (m, 3H), 7.99 (d,
(3ah). Yellow oil: Rf¼0.13 (5:1 petroleum ether/EtOAc); 1H NMR
J¼9.2 Hz, 1H), 7.38 (d, J¼9.2 Hz, 1H), 7.25 (m, 1H), 4.11 (s, 3H); 13C
(300 MHz, CDCl3)
d
8.08 (dd, J¼4.5,1.2 Hz,1H), 7.42 (td, J¼7.2,1.8 Hz,
NMR (100 MHz, CDCl3) d 177.2, 153.8, 151.1, 142.8, 141.9, 137.0, 136.4,
1H), 6.55 (t, J¼5.7 Hz,1H), 6.37 (d, J¼8.4 Hz, 1H), 5.53 (s, 1H), 4.50 (s,
1H), 3.30 (dd, J¼12.3, 6.9 Hz, 2H), 2.27 (t, J¼6.6 Hz, 2H),1.98 (m, 4H),
124.4, 118.0, 117.8, 117.4, 85.5, 31.1; LRMS (EI) 335 (M); HRMS (EI)
calcd for C13H9IN2O (M) 335.9760, found 335.9765; IR (KBr, cmꢁ1
3083 (w), 2954 (m), 2915 (m), 2869 (w), 1635 (m), 1585 (s).
)
1.60 (m, 4H); 13C NMR (75 MHz, CDCl3)
d 159.0, 148.4, 137.6, 134.8,
124.0, 112.8, 106.6, 39.9, 37.8, 28.0, 25.4, 23.0, 22.6; LRMS (EI) 202
(M); HRMS (EI) calcd for C13H18N2 (M) 202.1470, found 202.1474.
4.4.4. 7-Bromo-10-methylbenzo[b][1,8]naphthyridin-5(10H)-one
(5ad). Yellow solid: mp 202e203 ꢀC; Rf¼0.18 (5:1 petroleum ether/
4.3.9. N,N-Dibenzylpyridin-2-amine (3ai). Yellow oil: Rf¼0.27 (20:1
EtOAcþ1% TEA); 1H NMR (400 MHz, CDCl3)
d 8.73 (m, 2H), 8.55 (s,
1H), 7.78 (d, J¼8.8 Hz, 1H), 7.46 (d, J¼8.8 Hz, 1H), 7.26 (m, 1H), 4.09
petroleum ether/EtOAc); 1H NMR (300 MHz, CDCl3)
d
8.20 (dt,
J¼5.1, 0.9 Hz, 1H), 7.31 (m, 11H), 6.58 (td, J¼5.1, 0.9 Hz, 1H), 6.45 (d,
(s, 3H); 13C NMR (100 MHz, CDCl3)
d 177.3, 153.8, 151.1, 141.3, 137.2,
J¼8.7 Hz, 1H), 4.79 (s, 4H); 13C NMR (75 MHz, CDCl3)
d
158.8, 148.2,
136.9, 130.1, 123.9, 118.0, 117.6, 117.2, 115.6, 31.1; LRMS (EI) 288 (M);
HRMS (EI) calcd for C13H9BrN2O (M) 287.9898, found 287.9904.
138.6, 137.6, 128.8, 127.2, 127.1, 112.4, 106.1, 51.0; LRMS (EI) 274 (M);
HRMS (EI) calcd for C19H18N2 (M) 274.1470, found 274.1473.
4.4.5. 7-Chloro-10-methylbenzo[b][1,8]naphthyridin-5(10H)-one
4.3.10. N-(4-Bromophenyl)quinolin-2-amine (3bj). Brown solid: mp
143e145 ꢀC; Rf¼0.56 (2:1 petroleum ether/EtOAc); 1H NMR
(5ae). Yellow solid: mp 210e212 ꢀC; Rf¼0.5 (2:1 petroleum ether/
EtOAcþ1% TEA); 1H NMR (400 MHz, CDCl3)
d 8.76 (m, 2H), 8.45 (s,
(400 MHz, CDCl3)
d
7.94 (d, J¼8.8 Hz, 1H), 7.80 (d, J¼8.0 Hz,1H), 7.61
1H), 7.68 (d, J¼9.2 Hz, 1H), 7.57 (d, J¼9.2 Hz, 1H), 7.25 (m, 1H), 4.13
(m, 4H), 7.46 (d, J¼8.8 Hz, 2H), 7.32 (t, J¼7.2 Hz, 1H), 6.90 (d,
(s, 3H); 13C NMR (100 MHz, CDCl3)
d 177.5, 153.8, 151.1, 141.0, 137.0,
J¼8.8 Hz, 1H), 6.75 (s, 1H); 13C NMR (100 MHz, CDCl3)
d
153.8, 147.6,
134.6, 128.2, 126.9, 123.6, 118.0, 117.4, 117.2, 31.2; LRMS (EI) 244 (M);
HRMS (EI) calcd for C13H9ClN2O (M) 244.0403, found 244.0408.
139.6, 138.0, 132.2, 130.1, 127.6, 127.1, 124.4, 123.7, 121.6, 115.2, 112.2;
LRMS (EI) 299 (M); HRMS (EI) calcd for C15H11BrN2 (M) 298.0106,
found 298.0111.
4.4.6. 8-Bromo-10-methylbenzo[b][1,8]naphthyridin-5(10H)-one
(5af). Yellow solid: mp 234e235 ꢀC; Rf¼0.4 (3:1 petroleum ether/
4.3.11. N-Methyl-N-[4-(pyridin-2-yloxy)butyl]aniline (3aa0). Yellow
oil: Rf¼0.49 (20:1 petroleum ether/EtOAc); 1H NMR (400 MHz,
EtOAcþ1% TEA); 1H NMR (400 MHz, CDCl3)
d 8.77 (m, 2H), 8.37 (d,
J¼8.8 Hz, 1H), 7.80 (s, 1H), 7.44 (d, J¼8.4 Hz, 1H), 7.28 (t, J¼6.0 Hz,
CDCl3)
d
8.14 (d, J¼4.0 Hz, 1H), 7.54 (td, J¼10.0, 4.0 Hz, 1H), 7.20 (m,
1H), 4.12 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 178.0, 153.7, 151.2,
2H), 6.84 (m, 1H), 6.69 (m, 4H), 4.31 (t, J¼6.0 Hz, 2H), 3.38 (t,
143.3, 136.9, 129.8, 129.3, 125.5, 121.4, 118.5, 118.1, 117.5, 31.1; LRMS
(EI) 288 (M); HRMS (EI) calcd for C13H9BrN2O (M) 287.9898, found
287.9901; IR (KBr, cmꢁ1) 3084 (w), 2951 (w), 2917 (m), 2870 (m),
2849 (w), 1637 (m), 1587 (m).
J¼8.0 Hz, 2H), 2.93 (s, 3H), 1.77 (m, 4H); 13C NMR (100 MHz, CDCl3)
d
164.1, 149.5, 147.0, 138.7, 129.3, 116.7, 116.2, 112.4, 111.3, 65.7, 52.7,
38.5, 26.9, 23.7; LRMS (ESI) 257 (MþH); HRMS (ESI) calcd for
C16H21N2O (MþH) 257.1648, found 257.1654; IR (KBr, cmꢁ1) 3091
(w), 2945 (m), 2884 (m), 2867 (m), 1596 (s), 1569 (m).
4.4.7. Methyl 10-methyl-5-oxo-5,10-dihydrobenzo[b][1,8]naphthyr-
idine-8-carboxylate (5ag). Yellow solid: mp 225e226 ꢀC; Rf¼0.12
(5:1 petroleum ether/EtOAcþ1% TEA); 1H NMR (400 MHz, CDCl3)
4.4. General procedure for the synthesis of
benzonaphthyridinones
d
8.78 (m, 2H), 8.56 (d, J¼8.0 Hz, 1H), 8.34 (s, 1H), 7.92 (d, J¼8.4 Hz,
1H), 7.27 (m,1H), 4.20 (s, 3H), 4.02 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 178.2, 166.4, 153.9, 151.4, 142.1, 136.9, 135.0, 128.1, 125.0, 122.0,
The benzonaphthyridinones were prepared from the corre-
sponding o-aminobenzoates and aryne precursors following the
same procedure used for the synthesis of 2-pyridinylamines. The
residue was purified by column chromatography (petroleum ether/
EtOAcþ1% TEA) to afford the benzonaphthyridinones.
118.0, 117.6, 117.5, 52.9, 31.2; LRMS (EI) 268 (M); HRMS (EI) calcd for
C15H12N2O3 (M) 268.0848, found 268.0854; IR (KBr, cmꢁ1) 3082 (w),
2954 (m), 2923 (m), 2871 (w), 1730 (s), 1638 (s), 1614 (m), 1593 (s).
4.4.8. 6-Methyldibenzo[b,g][1,8]naphthyridin-11(6H)-one (5ba).-
Yellow solid: mp 229e231 ꢀC; Rf¼0.27 (5:1 petroleum ether/
4.4.1. 10-Methylbenzo[b][1,8]naphthyridin-5(10H)-one
(5aa). Yellow solid: mp 214e215 ꢀC; Rf¼0.24 (3:1 petroleum ether/
EtOAcþ1% TEA); 1H NMR (400 MHz, CDCl3)
d 9.32 (s, 1H), 8.53 (d,
J¼7.6 Hz, 1H), 8.00 (m, 2H), 7.80 (m, 2H), 7.60 (d, J¼8.4 Hz, 1H),
EtOAcþ1% TEA); 1H NMR (300 MHz, CDCl3)
d
8.79 (m, 2H), 8.55 (dd,
J¼8.1, 1.5 Hz, 1H), 7.79 (td, J¼7.2, 1.5 Hz, 1H), 7.63 (d, J¼8.4 Hz, 1H),
7.47 (t, J¼7.6 Hz, 1H), 7.31 (t, J¼7.6 Hz, 1H), 4.22 (s, 3H); 13C NMR
7.35 (t, J¼7.5 Hz, 1H), 7.25 (m, 1H), 4.15 (s, 3H); 13C NMR (75 MHz,
(100 MHz, CDCl3)
d 179.7, 157.1, 150.1, 143.7, 139.2, 135.2, 132.8,
CDCl3)
d
178.6, 153.5, 151.3, 142.6, 137.0, 134.6, 127.8, 122.8, 122.1,
129.7, 128.1, 127.8, 124.8, 122.4, 121.6, 121.5, 117.8, 115.4, 31.0;
LRMS (EI) 260 (M); HRMS (EI) calcd for C17H12N2O (M) 260.0950,
found 260.0955; IR (KBr, cmꢁ1) 3064 (w), 2954 (w), 2917 (m),
2871 (m), 2850 (w), 1608 (s).
117.6, 117.4, 115.6, 31.0; LRMS (EI) 210 (M), 209 (MꢁH); HRMS (EI)
calcd for C13H10N2O (M) 210.0793, found 210.0796.
4.4.2. 10-Allyl-8-bromobenzo[b][1,8]naphthyridin-5(10H)-one
(5ab). Yellow solid: mp 145e146 ꢀC; Rf¼0.25 (5:1 petroleum ether/
4.4.9. 5H-Thiochromeno[2,3-b]pyridin-5-one (5ai). White solid:
mp 236e238 ꢀC (lit.24 233e234 ꢀC); Rf¼0.24 (5:1 petroleum
EtOAcþ1% TEA); 1H NMR (400 MHz, CDCl3)
8.78 (d, J¼6.4 Hz, 2H),
d
8.38 (d, J¼8.4 Hz, 1H), 7.71 (s, 1H), 7.43 (d, J¼8.4 Hz, 1H), 7.29 (m,
1H), 6.08 (m, 1H), 5.41 (s, 2H), 5.26 (d, J¼10.0 Hz, 1H), 5.07 (d,
ether/EtOAc); 1H NMR (400 MHz, CDCl3)
d 8.83 (m, 2H), 8.60 (d,
J¼8.0 Hz, 1H), 7.70 (m, 2H), 7.53 (td, J¼8.0, 1.6 Hz, 1H), 7.46 (dd,
J¼17.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
178.0, 154.0, 150.9,
J¼8.0, 4.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 180.8, 158.9, 153.5,