ACCEPTED MANUSCRIPT
3.5 Hz, 2H), 8.00 (d, J = 2.4 Hz, 1H), 7.96 (dd, J = 8.7, 1.8 Hz, 1H), 7.90 (t, J = 7.9 Hz, 1H),
7.80 (d, J = 8.0 Hz, 1H), 7.06 (dd, J = 8.9, 2.6 Hz, 1H), 6.93 (t, J = 5.6 Hz, 2H), 6.57 (d, J = 8.9
Hz, 1H), 3.05 (s, 6H). 13C NMR (101 MHz, DMSO-D6) δ(ppm): 163.12, 158.83, 150.85, 148.29,
146.25, 142.17, 141.98, 140.82, 135.40, 135.28, 133.89, 132.03, 131.59, 131.39, 131.26, 128.31,
127.14, 126.64, 122.30, 122.18, 121.11, 117.99, 114.08, 105.82, 38.10. HR-MS (ESI) m/z: calcd.
for C26H19F3N4O [M + H]+: 461.1511, found: 461.1585. Mp 220–222 °C.
General procedure for the preparation of 9-((3-aminophenyl)amino)-1-(3-(trifluoromethyl)
phenyl)benzo[h][1,6]naphthyridin-2(1H)-one(4c) To a solution of compound 3 (4.18 g, 10
mmol) in 1,4-dioxane at room temperature, we subsequently added Pd(dba)3 (0.23 g, 0.25 mmol),
CsCO3 (4.88 g, 15 mmol), 1,3-phenylenediamineand (1.62 g, 15 mmol) and 4,5-Bis
(diphenylphosphino)-9,9-dimethylxanthene (0.14 g, 0.25 mmol). The resulting mixture was
heated to 100 °C for 2 h under a N2 atmosphere. The solution was extracted with EtOAc. The
organic layer was washed with water and brine, dried (MgSO4), filtered, and evaporated to
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dryness as a yellow solid. (3.52 g, 78.8% yield). H NMR (400 MHz, DMSO-D6) δ(ppm): 8.85
(s, 1H), 8.22 (d, J = 9.5 Hz, 1H), 7.94 (s, 1H), 7.86 (d, J = 9.0 Hz, 1H), 7.78 (d, J = 8.1 Hz, 1H),
7.63 (dd, J = 14.4, 6.4 Hz, 2H), 7.53 (d, J = 7.9 Hz, 1H), 7.29 (dd, J = 9.0, 2.4 Hz, 1H), 6.89 –
6.80 (m, 2H), 6.43 (d, J = 2.3 Hz, 1H), 6.21 (dd, J = 7.9, 1.3 Hz, 1H), 6.07 (t, J = 2.0 Hz, 1H),
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5.87 – 5.75 (m, 1H), 5.15 (s, 2H). C NMR (101 MHz, DMSO-D6) δ(ppm): 163.08, 149.72,
147.18, 144.29, 142.66, 142.42, 140.96, 140.81, 140.76, 133.62, 131.57, 131.43, 130.78, 130.47,
130.08, 125.39, 123.80, 122.80, 121.75, 118.98, 114.25, 108.69, 107.17, 105.64, 105.16. HR-MS
(ESI) m/z: calcd. for C25H17F3N4O [M + H]+: 447.1354, found: 447.1427. Mp 217–218 °C.
9-((6-aminopyridin-2-yl)amino)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1
H)-one (4d) The title compound was obtained similarly to 4c. 1,3-phenylenediamineand was
replaced with pyridine-2,6-diamine. (yellow solid, yield: 81.3%). 1H NMR (400 MHz,
DMSO-D6) δ(ppm): 8.91 (s, 1H), 8.50 (s, 1H), 8.25 (d, J = 9.5 Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H),
7.87 (d, J = 9.0 Hz, 1H), 7.66 (dt, J = 13.4, 7.8 Hz, 3H), 7.52 (dd, J = 9.0, 2.3 Hz, 1H), 7.22 –
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7.11 (m, 2H), 6.86 (d, J = 9.4 Hz, 1H), 5.91 (d, J = 7.9 Hz, 1H), 5.71 (t, J = 14.5 Hz, 3H). C
NMR (101 MHz, DMSO-D6) δ(ppm): 163.02, 148.31, 141.68, 141.18, 140.71, 134.17, 131.40,
130.91, 130.87, 130.58, 125.83, 125.80, 125.66, 125.63, 125.51, 125.11, 122.80, 122.05, 120.74,
118.47, 114.24, 114.22, 100.00, 97.26. HR-MS (ESI) m/z: calcd. for C24H16F3N5O [M + H]+:
448.1307, found: 448.1380. Mp 259–261 °C.
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