Full Paper
N-(3-Bromopyridin-4-yl)-N,2-dimethyl-1,3-oxazole-4-carb-
oxamide (32a): The general procedure using 31a gave, after chro-
5-Butyl-2-methyl[1,3]oxazolo[4,5-c]-1,8-naphthyridin-4(5H)-one
(33c): The general procedure (conditions [b]) gave, after chromato-
graphic purification (dichloromethane/diethyl ether, 95:5), 33c
matographic purification (heptane/ethyl acetate, 2:8), 32a (0.096 g,
1
1
1
6 %) as a colourless oil. H NMR (400 MHz, CDCl ): δ = 8.80 (s, 1
(195 mg, 76 %) as a white solid. M.p. 149–152 °C. H NMR (300 MHz,
3
H), 8.55 (d, J = 5.1 Hz, 1 H), 7.69 (s, 1 H), 7.23 (d, J = 5.1 Hz, 1 H),
CDCl ): δ = 8.65 (dd, J = 4.7, 1.9 Hz, 1 H), 8.17 (dd, J = 7.8, 1.9 Hz,
3
1
3
3
1
1
1
1
.39 (s, 3 H), 2.27 (s, 3 H) ppm. C NMR (101 MHz, CDCl ): δ = 1 H), 7.27 (dd, J = 7.8, 4.7 Hz, 1 H), 4.65–4.57 (m, 2 H), 2.71 (s, J =
3
61.22, 160.71, 153.40, 150.55, 149.77, 142.39, 135.74, 124.61,
4.0 Hz, 3 H), 1.81–1.67 (m, 2 H), 1.54–1.36 (m, 2 H), 0.96 (t, J = 7.3 Hz,
21.20, 36.87, 13.68 ppm. IR (ATR diamond): ν˜ = 1642, 1587, 1566, 3 H) ppm. 13C NMR (75 MHz, CDCl ): δ = 163.61, 157.28, 150.70,
3
485, 1423, 1402, 1365, 1324, 1307, 1282, 1237, 1200, 1172, 1110,
149.38, 147.92, 129.90, 129.37, 117.89, 106.93, 41.47, 30.35, 20.23,
14.28, 13.90 ppm. IR (ATR diamond): ν˜ = 1672, 1589, 1578, 1556,
1486, 1437, 1393, 1375, 1346, 1304, 1283, 1267, 1236, 1187, 1118,
–
1
084, 1039, 1021 cm . HRMS (ESI): calcd. for C H BrN O [M +
1
1
11
3 2
+
H] 296.0029; found 296.0034.
–
1
1
+
105, 1064, 1035, 1003 cm . HRMS (ESI): calcd. for C H N O [M
14 16 3 2
N-(3-Bromopyridin-4-yl)-N-methyl-2-phenyl-1,3-oxazole-4-
carboxamide (32b): The adapted general procedure using 31b
+
H] 258.1237; found 258.1237.
(
1.377 g, 4.00 mmol) gave, after chromatographic purification (hept- 5-Butyl-2-phenyl[1,3]oxazolo[4,5-c]-1,8-naphthyridin-4(5H)-one
1
ane/ethyl acetate, 5:5), 32b (0.209 g, 15 %) as a colourless oil. H
(33d): The general procedure (conditions [b]) gave, after chromato-
graphic purification (dichloromethane/diethyl ether, 9:1), 33d
(267 mg, 84 %) as a white solid. M.p. 151–152 °C. H NMR (400 MHz,
NMR (400 MHz, CDCl ): δ = 8.84 (s, 1 H), 8.59 (d, J = 5.1 Hz, 1 H),
3
1
8
.09 (s, 1 H), 7.64 (s, 2 H), 7.50–7.32 (m, 3 H), 7.30 (d, J = 5.1 Hz, 1
13
H), 3.42 (s, 3 H) ppm. C NMR (101 MHz, CDCl ): δ = 160.92, 160.60,
CDCl
7.48 (m, 3 H), 7.30 (dd, J = 7.8, 4.7 Hz, 1 H), 4.80–4.55 (m, 2 H), 1.83–
3
): δ = 8.67 (dd, J = 4.7, 1.8 Hz, 1 H), 8.32–8.24 (m, 3 H), 7.57–
3
1
1
1
1
3
53.21, 150.72, 149.68, 143.13, 136.99, 130.86, 128.80, 126.50,
1
3
26.39, 124.70, 121.57, 36.78 ppm. IR (ATR diamond): ν˜ = 1645, 1561, 1.69 (m, 2 H), 1.59–1.37 (m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H) ppm.
C
481, 1449, 1422, 1399, 1367, 1332, 1260, 1205, 1175, 1112, 1080,
057, 1022 cm–1. HRMS (ESI): calcd. for C16H13BrN O [M + H]
NMR (101 MHz, CDCl ): δ = 163.28, 157.58, 150.49, 149.60, 148.16,
3
+
131.77, 130.99, 129.60, 129.00, 127.44, 126.19, 118.02, 107.04, 41.62,
3
2
58.0186; found 358.185.
30.40, 20.27, 13.96 ppm. IR (ATR diamond): ν˜ = 1685, 1587, 1574,
1
1
556, 1493, 1441, 1390, 1371, 1346, 1317, 1303, 1283, 1254, 1232,
General Procedure for Intramolecular C–H Arylation To Give Tri-
cyclic Scaffolds
–
1
191, 1148, 1124, 1066, 1024 cm . HRMS (ESI): calcd. for
+
C H N O [M + H] 320.1394; found 320.1389.
19 18 3 2
Conditions [a]: Bromopyridine (1.00 mmol), [Pd(PPh ) ]
3
4
5
-Benzyl-2-methyl[1,3]oxazolo[4,5-c]-1,8-naphthyridin-4(5H)-
(0.05 mmol), and KOAc (1.50 mmol) were combined in DMA (7 mL;
one (33e): The general procedure (conditions [b]) gave, after chro-
0
.143
M), and the mixture was stirred under nitrogen at 140 °C for
matographic purification (dichloromethane/diethyl ether, 95:5), 33e
18 h. The reaction mixture was then concentrated in vacuo. The
1
(
245 mg, 84 %) as a white solid. M.p. 172–175 °C. H NMR (300 MHz,
residue was suspended in CH Cl and purified by silica gel chroma-
2
2
CDCl ): δ = 8.62 (dd, J = 4.7, 1.8 Hz, 1 H), 8.13 (dd, J = 7.8, 1.8 Hz,
3
tography to give products 33.
1
H), 7.54–7.46 (m, 2 H), 7.28–7.13 (m, 4 H), 5.85 (s, 2 H), 2.70 (s, 3
1
3
Conditions [b]: Bromopyridine (1.00 mmol), Pd(OAc) (0.05 mmol),
H) ppm. C NMR (75 MHz, CDCl ): δ = 163.81, 157.53, 150.97,
2
3
PPh3 resin (83 mg, corresponding to a PPh3 loading of 0.10–
149.42, 147.95, 137.76, 130.02, 129.51, 128.70, 128.19, 127.16,
0
.13 mmol), and KOAc (1.50 mmol) were combined in N,N-dimethyl-
118.27, 107.09, 44.35, 14.33 ppm. IR (ATR diamond): ν = 1681, 1580,
˜
acetamide (7 mL; 0.143
M), and the mixture was stirred under nitro- 1550, 1495, 1484, 1438, 1407, 1386, 1375, 1350, 1305, 1269, 1258,
–
1
gen at 160 °C for 18 h. The reaction mixture was then concentrated 1224, 1173, 1130, 1108, 1069, 1028, 1009 cm . HRMS (ESI): calcd.
in vacuo. The residue was suspended in dichloromethane and puri-
+
for C H N O [M + H] 292.1081; found 292.1086.
1
7 14 3 2
fied by silica gel chromatography to give products 33.
5
-Benzyl-2-phenyl[1,3]oxazolo[4,5-c]-1,8-naphthyridin-4(5H)-
2
(
,5-Dimethyl[1,3]oxazolo[4,5-c]-1,8-naphthyridin-4(5H)-one
33a): The general procedure (conditions [b]) gave, after chromato-
graphic purification (dichloromethane/diethyl ether, 92:8), 33a
one (33f): The general procedure (conditions [b]) gave, after chro-
matographic purification (dichloromethane/diethyl ether, 95:5), 33f
(315 mg, 89 %) as a white solid. M.p. 232–235 °C. H NMR (400 MHz,
1
1
(110 mg, 73 %) as a white solid. M.p. 218–219 °C. H NMR (300 MHz,
CDCl ): δ = 8.63 (dd, J = 4.7, 1.8 Hz, 1 H), 8.32–8.18 (m, 3 H), 7.60–
3
1
3
CDCl ): δ = 8.66 (dd, J = 4.7, 1.8 Hz, 1 H), 8.18 (dd, J = 7.8, 1.8 Hz,
7.42 (m, 5 H), 7.31–7.14 (m, 4 H), 5.87 (s, 2 H) ppm. C NMR
3
1
H), 7.29 (dd, J = 7.8, 4.8 Hz, 1 H), 3.92 (s, 3 H), 2.72 (s, 3 H) ppm.
(101 MHz, CDCl ): δ = 163.37, 157.74, 150.66, 149.56, 148.06, 137.70,
3
1
3
C NMR (75 MHz, CDCl ): δ = 163.75, 157.70, 150.79, 149.34, 148.30, 131.80, 131.01, 129.66, 128.99, 128.85, 128.20, 127.40, 127.23,
3
1
29.92, 129.45, 118.05, 107.03, 28.86, 14.32 ppm. IR (ATR diamond):
126.05, 118.35, 107.10, 44.41 ppm. IR (ATR diamond): ν = 1680, 1606,
˜
ν = 1671, 1581, 1440, 1377, 1349, 1324, 1309, 1263, 1233, 1212,
1577, 1556, 1495, 1440, 1389, 1348, 1321, 1300, 1280, 1255, 1243,
˜
–
1
–1
1
134, 1104, 1063, 1022, 1009 cm . HRMS (ESI): calcd. for 1160, 1136, 1107, 1079, 1055, 1024 cm . HRMS (ESI): calcd. for
+
+
C H N O [M + H] 216.0768; found 216.0770.
C H N O [M + H] 354.1237; found 354.1228.
11
10
3
2
22 16 3 2
5
-Methyl-2-phenyl[1,3]oxazolo[4,5-c]-1,8-naphthyridin-4(5H)-
2,5-Dimethyl[1,3]oxazolo[4,5-c]-1,5-naphthyridin-4(5H)-one
(33g): The general procedure (conditions [a]) gave, after chromato-
graphic purification (dichloromethane/diethyl ether, 8:2 until the tri-
phenylphosphine oxide was removed, then dichloromethane/meth-
one (33b): The general procedure (conditions [b]) gave, after chro-
matographic purification (dichloromethane/diethyl ether, 9:1), 33b
(
232 mg, 84 %) as a pale orange solid. M.p. 268–270 °C. 1H NMR
(
3
400 MHz, CDCl ): δ = 8.69 (dd, J = 4.7, 1.8 Hz, 1 H), 8.36–8.23 (m,
anol, 97:3), 33g (208 mg, 97 %) as a pale yellow solid. M.p. 242–
3
1
H), 7.60–7.48 (m, 3 H), 7.33 (dd, J = 7.8, 4.7 Hz, 1 H), 3.97 (s, 3 H)
243 °C. H NMR (400 MHz, CDCl ): δ = 8.63 (d, J = 4.4 Hz, 1 H), 7.83
3
13
ppm. C NMR (101 MHz, CDCl ): δ = 163.40, 157.97, 150.57, 149.55, (d, J = 8.7 Hz, 1 H), 7.56 (dd, J = 8.6, 4.5 Hz, 1 H), 3.83 (s, 3 H), 2.75
3
1
1
1
1
2
48.53, 131.84, 131.02, 129.66, 129.02, 127.49, 126.15, 118.18,
(s, 3 H) ppm. 13C NMR (101 MHz, CDCl ): δ = 164.63, 156.79, 151.54,
3
07.11, 29.04 ppm. IR (ATR diamond): ν˜ = 1673, 1575, 1557, 1498, 144.63, 135.02, 132.54, 129.48, 124.13, 122.56, 29.41, 14.32 ppm. IR
480, 1447, 1385, 1351, 1333, 1285, 1259, 1218, 1150, 1109, 1067, (ATR diamond): ν˜ = 1670, 1626, 1581, 1494, 1461, 1398, 1382, 1354,
050, 1023 cm–1. HRMS (ESI): calcd. for C16H12N O [M + H]
+
1316, 1271, 1235, 1213, 1113, 1053 cm . HRMS (ESI): calcd. for
–1
3
2
+
78.0924; found 278.0933.
C H N O [M + H] 216.0768; found 216.0747.
1
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Eur. J. Org. Chem. 2017, 1465–1474
www.eurjoc.org
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© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim