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H. Tan et al. / Tetrahedron 69 (2013) 8299e8304
4.4. General procedure for the synthesis of substituted 2,7-
naphthyridinones (8)
125.26, 122.19, 115.96, 101.51, 64.64, 56.20. HRMS (ESI): m/z calcd for
C
22H18N2O2 [MþH]þ: 343.14410. Found: 343.14381.
To a mixture of the arylethanones (1.5 mmol) and sodium
tert-butoxide (0.240 g, 2.5 mmol) in THF (5 mL) at ꢁ20 ꢀC,
1-benzyl-3-carbamoylpyridinium chloride (0.249 g, 1.0 mmol)
was added gradually, under stirring. After 2 h, formic acid (4 mL)
was added in the mixture and refluxed for 0.5 h. Then the solvent
was evaporated under reduced pressure, and the residue was
purified by silica gel column to afford the corresponding prod-
ucts 8.
4.4.7. 7-Benzyl-3-(4-bromophenyl)-2,7-naphthyridin-1(7H)-one
(8g). Yellow solid. Mp: 163e165 ꢀC. 1H NMR (400 MHz, DMSO):
d
9.83 (s, 1H), 8.91 (d, J¼6.6 Hz, 1H), 8.17 (d, J¼6.7 Hz, 1H), 7.90e7.76
(m, 4H), 7.57e7.55 (m, 2H), 7.47e7.45 (m, 3H), 7.24 (s, 1H), 5.89 (s,
2H). 13C NMR (100 MHz, DMSO):
166.30, 161.71, 146.26, 145.91,
d
138.27, 137.60, 135.45, 131.65, 129.67, 129.32, 129.11, 128.61, 124.01,
122.30, 117.99, 97.79, 61.41. HRMS (ESI): m/z calcd for C21H15BrN2O
[MþH]þ: 341.12845. Found: 391.04356.
4.4.1. 7-Benzyl-3-phenyl-2,7-naphthyridin-1(7H)-one (8a). Yellow
4.4.8. 7-Benzyl-3-(4-fluorophenyl)-2,7-naphthyridin-1(7H)-one
(8h). Yellow solid. Mp: 148e150 ꢀC. 1H NMR (400 MHz, MeOD):
solid. Mp: 133e135 ꢀC. 1H NMR (400 MHz, MeOD):
d 9.85 (s, 1H),
8.91 (d, J¼6.7 Hz, 1H), 8.16 (d, J¼6.8 Hz, 1H), 7.93e7.86 (m, 2H),
d
9.63 (s, 1H), 8.74 (d, J¼6.8 Hz, 1H), 8.10 (d, J¼6.8 Hz, 1H), 7.91
7.63e7.56 (m, 5H), 7.51e7.37 (m, 3H), 7.24 (s, 1H), 5.71 (d,
(dd, J¼5.2, 8.5 Hz, 2H), 7.55 (d, J¼6.0 Hz, 2H), 7.49e7.46 (m, 3H),
J¼147.7 Hz, 2H). 13C NMR (100 MHz, MeOD):
d 162.34, 155.42,
7.32 (t, J¼8.6 Hz, 2H), 7.10 (s, 1H), 5.85 (s, 2H). 13C NMR
150.30, 147.44, 143.45, 134.88, 133.06, 130.94, 130.72, 130.51, 130.15,
128.77, 125.61, 122.91, 111.39, 102.64, 64.83. HRMS (ESI): m/z calcd
for C21H16N2O [MþH]þ: 313.13354. Found: 313.13320.
(100 MHz, MeOD):
d
166.24 (d, JFC¼251.9 Hz), 162.95, 155.02,
150.04, 147.38, 143.18, 134.92, 131.41, 131.32, 130.90, 130.69,
130.14, 125.49, 122.55, 117.43 (d, JFC¼22.4 Hz), 102.50, 64.78.
HRMS (ESI): m/z calcd for
C
21H15FN2O [MþH]þ: 331.12412.
4.4.2. 7-Benzyl-3-(3-methoxyphenyl)-2,7-naphthyridin-1(7H)-one
Found: 331.12358.
(8b). Yellow solid. Mp: 128e129 ꢀC. 1H NMR (400 MHz, MeOD):
d
9.64 (s, 1H), 8.77 (d, J¼6.2 Hz, 1H), 8.45 (s, 1H), 8.12 (d, J¼6.2 Hz,
1H), 7.55e7.38 (m, 7H), 7.18 (d, J¼7.7 Hz, 1H), 7.14 (s, 1H), 5.85 (s,
2H), 3.90 (s, 3H). 13C NMR (100 MHz, MeOD):
171.19, 161.72,
4.4.9. 7-Benzyl-3-(3-nitrophenyl)-2,7-naphthyridin-1(7H)-one
(8i). Yellow solid. Mp: 170e171 ꢀC. 1H NMR (400 MHz, MeOD):
d
d
9.54 (s, 1H), 8.75 (s, 1H), 8.60 (d, J¼6.8 Hz, 1H), 8.34 (d, J¼8.2 Hz,
155.23, 150.22, 147.42, 143.44, 135.14, 134.92, 131.67, 130.93, 130.71,
130.18, 125.63, 122.92, 120.94, 118.71, 113.99, 102.74, 64.79, 56.08.
HRMS (ESI): m/z calcd for C22H18N2O2 [MþH]þ: 343.14410. Found:
343.14364.
1H), 8.29 (d, J¼7.8 Hz, 1H), 8.02 (d, J¼8.4 Hz, 1H), 7.75 (t, J¼8.0 Hz,
1H), 7.55e7.43 (m, 5H), 7.21 (s, 1H), 5.81 (s, 2H). 13C NMR (100 MHz,
MeOD):
d 166.53, 157.57, 149.97, 149.16, 147.50, 141.58, 138.42,
135.14, 134.70, 131.45, 130.82, 130.67, 130.03, 126.35, 125.21, 123.68,
121.66, 102.64, 64.63. HRMS (ESI): m/z calcd for C21H15N3O3
[MþH]þ: 358.11862. Found: 358.11810.
4.4.3. 3-(Benzo[d][1,3]dioxol-5-yl)-7-benzyl-2,7-naphthyridin-
1(7H)-one (8c). Yellow solid. Mp: 125e126 ꢀC. 1H NMR (400 MHz,
MeOD):
d
9.32 (s, 1H), 8.32 (d, J¼6.8 Hz, 1H), 7.79 (d, J¼6.9 Hz, 1H),
4.4.10. 7-Benzyl-3-(4-nitrophenyl)-2,7-naphthyridin-1(7H)-one
7.55 (dd, J¼8.2, 1.5 Hz, 1H), 7.51e7.42 (m, 7H), 7.03 (s, 1H), 6.91 (d,
(8j). Yellow solid. Mp: 172e173 ꢀC. 1H NMR (400 MHz, MeOD):
J¼8.2 Hz, 1H), 6.03 (s, 2H), 5.67 (s, 2H). 13C NMR (100 MHz, MeOD):
d
9.39 (s, 1H), 8.36e8.27 (m, 5H), 7.88 (d, J¼6.9 Hz, 1H), 7.53e7.41
d
169.08, 162.64, 151.63, 149.79, 148.22, 147.07, 139.71, 135.49,
(m, 5H), 5.71 (s, 2H). 13C NMR (100 MHz, MeOD):
d
172.46, 164.25,
132.27, 130.64, 130.60, 129.83, 124.12, 123.90, 119.70, 109.43, 108.84,
103.21, 101.07, 64.04. HRMS (ESI): m/z calcd for C22H16N2O3
[MþH]þ: 357.12337. Found: 357.12359.
150.07, 147.81, 147.59, 146.74, 138.77, 135.62, 130.60, 129.97, 129.82,
124.63, 124.35, 119.28, 111.40, 102.20, 64.11 HRMS (ESI): m/z calcd
for C21H15N3O3 [MþH]þ: 358.11862. Found: 358.11876.
4.4.4. 7-Benzyl-3-p-tolyl-2,7-naphthyridin-1(7H)-one (8d). Yellow
4.4.11. 7-Benzyl-3-(4-chlorophenyl)-2,7-naphthyridin-1(7H)-one
solid. Mp: 138e140 ꢀC. 1H NMR (400 MHz, MeOD):
d
9.55 (s, 1H),
(8k). Yellow solid. Mp: 151e152 ꢀC. 1H NMR (400 MHz, MeOD):
8.61 (s, 1H), 8.01 (s, 1H), 7.78 (d, J¼7.5 Hz, 1H), 7.58e7.35 (m, 5H),
d
9.44 (s, 1H), 8.48 (d, J¼6.4 Hz, 1H), 8.00e7.81 (m, 3H), 7.61e7.44
(m, 7H), 7.10 (s, 1H), 5.74 (s, 2H). 13C NMR (100 MHz, MeOD):
d 167.76, 160.28, 148.74, 147.31, 140.73, 138.13, 136.09, 135.29,
7.39 (d, J¼7.5 Hz, 1H), 7.09 (s, 1H), 5.78 (s, 2H), 2.43 (s, 3H). 13C NMR
(100 MHz, DMSO):
d
167.88, 162.42, 154.57, 147.78, 146.22, 141.88,
141.76, 134.83, 130.36, 129.77, 129.35, 128.84, 127.77, 123.79, 120.52,
100.20, 62.24, 21.10. HRMS (ESI): m/z calcd for C22H18N2O [MþH]þ:
327.14919. Found: 327.14906.
130.73, 130.63, 130.43, 130.14, 129.95, 124.71, 120.69, 101.87, 64.35.
HRMS (ESI): m/z calcd for C21H15ClN2O [MþH]þ: 347.09457. Found:
347.09393.
4.4.5. 7-Benzyl-3-(3,4,5-trimethoxyphenyl)-2,7-naphthyridin-1(7H)-
4.4.12. 7-Benzyl-3-(4-cyanophenyl)-2,7-naphthyridin-1(7H)-one
one (8e). Yellow solid. Mp: 108e110 ꢀC. 1H NMR (400 MHz,
(8l). Yellow solid. Mp: 145e147 ꢀC. 1H NMR (400 MHz, DMSO):
MeOD):
7.54e7.47 (m, 5H), 7.18 (s, 1H), 7.12 (s, 1H), 5.77 (s, 2H), 3.93 (s,
6H), 3.82 (s, 3H). 13C NMR (100 MHz, MeOD):
165.45, 162.69,
d
9.45 (s, 1H), 8.54 (d, J¼8.0 Hz, 1H), 7.94 (d, J¼8.0 Hz, 1H),
d
9.44 (s, 1H), 8.50 (d, J¼6.8 Hz, 1H), 8.22 (d, J¼8.5 Hz, 2H), 7.96 (d,
J¼8.3 Hz, 2H), 7.86 (d, J¼6.9 Hz, 1H), 7.5e7.39 (m, 5H), 7.17 (s, 1H),
5.76 (s, 2H). 13C NMR (100 MHz, DMSO):
167.86, 160.04, 146.50,
d
d
158.57, 154.88, 149.21, 147.15, 141.61, 135.11, 131.23, 130.83, 130.68,
130.08, 124.82, 121.32, 106.36, 101.99, 64.47, 61.22, 56.84. HRMS
(ESI): m/z calcd for C24H22N2O4 [MþH]þ: 403.16523. Found:
403.16467.
146.04, 142.33, 138.72, 135.27, 132.61, 129.30, 129.13, 128.62, 128.32,
122.69, 118.79, 118.73, 112.45, 98.76, 61.62. HRMS (ESI): m/z calcd
for C22H15N3O [MþH]þ: 338.12879. Found: 338.12875.
4.4.13. 7-Benzyl-3-(4-methoxycarbonylphenyl)-2,7-naphthyridin-
4.4.6. 7-Benzyl-3-(4-methoxyphenyl)-2,7-naphthyridin-1(7H)-one
1(7H)-one (8m). Yellow solid. Mp: 136e137 ꢀC. 1H NMR (400 MHz,
(8f). Yellowsolid. Mp: 108e110 ꢀC.1H NMR (400 MHz, MeOD):
d
9.58
MeOD):
8.15 (d, J¼5.6 Hz, 1H), 7.94 (d, J¼8.0 Hz, 2H), 7.55e7.47 (m, 5H), 7.17
(s, 1H), 3.95 (s, 3H). 13C NMR (100 MHz, MeOD):
167.41, 162.12,
d
9.68 (s, 1H), 8.80 (d, J¼5.6 Hz, 1H), 8.19 (d, J¼8.0 Hz, 2H),
(s,1H), 8.71 (d, J¼6.5 Hz,1H), 8.06 (d, J¼6.5 Hz,1H), 7.81 (d, J¼8.4 Hz,
2H), 7.56e7.46 (m, 5H), 7.10 (d, J¼8.4 Hz, 2H), 7.07 (s,1H), 5.83 (s, 2H),
d
3.87 (s, 3H). 13C NMR (100 MHz, MeOD):
d
164.43, 162.39, 155.06,
153.92, 150.21, 147.50, 143.75, 137.93, 134.80, 134.11, 131.30, 130.98,
130.73, 130.67, 130.20, 129.06, 125.91, 123.39, 103.48, 64.99, 53.02.
150.13, 147.20, 143.18, 134.95, 130.88, 130.68, 130.53, 130.13, 125.51,