Journal of Medicinal Chemistry
ARTICLE
provide 84% yield as a white crystal, mp = 316ꢀ319 °C. 1H NMR (400
MHz, DMSO) δ 11.25 (s, 1H), 8.04ꢀ7.97 (m, 1H), 7.66 (ddd, J = 8.7,
2.3, 1.4 Hz, 1H), 7.40 (dd, J = 8.7, 0.8 Hz, 1H), 2.67 (t, J = 5.9 Hz, 2H),
2.43 (t, J = 6.0 Hz, 2H), 1.77ꢀ1.67 (m, 4H), 1.32 (s, 9H). 13C NMR
(101 MHz, DMSO) δ 175.97, 146.32, 144.25, 137.30, 129.03, 122.64,
119.78, 117.19, 115.17, 34.27, 31.14, 27.07, 21.93, 21.72, 21.53. HRMS
(ESI) calcd for C17H22NO [M þ H]þ, 256.1696; found, 256.1700.
5-(Trifluoromethyl)-1,2,3,4-tetrahydroacridin-9(10H)-one
(60). Following general procedure C, the title compound was prepared
to provide 39% yield as a yellow powder, mp = 226ꢀ230 °C. 1H NMR
(400 MHz, DMSO) δ 10.00 (s, 1H), 8.40 (d, J = 7.9 Hz, 1H), 7.99 (d, J =
7.3 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H), 2.84 (s, 2H), 2.44 (s, 2H), 1.72 (dd,
J = 14.8, 6.6 Hz, 4H). 19F NMR (376 MHz, DMSO) δ ꢀ59.13. 13C
NMR (101 MHz, DMSO) δ 175.18, 148.45, 135.21, 130.51, 129.57 (d, J
= 5.05 Hz), 124.41, 123.79 (d, J = 276.7 Hz), 121.42, 117.16, 27.61,
21.59, 21.43. HRMS (ESI) calcd for C14H13F3NO [M þ H]þ,
268.0944; found, 268.0940.
provide 31% yield as a white powder, mp = 292ꢀ294 °C. 1H NMR (400
MHz, DMSO) δ 10.97 (s, 1H), 7.06 (s, 1H), 6.74 (s, 1H), 2.79 (s, 3H),
2.64 (s, 2H), 2.38 (s, 2H), 2.34 (s, 3H), 1.72 (br d, J = 15.4 Hz, 4H). 13C
NMR (101 MHz, DMSO) δ 178.28, 144.84, 141.08, 139.66, 138.73,
126.06, 119.63, 116.40, 114.83, 26.72, 23.18, 22.04, 21.74, 21.52, 21.01.
HRMS (ESI) calcd for C15H18NO [M þ H]þ, 228.1383; found,
228.1381.
5,6-Dimethyl-1,3,4,10-tetrahydro-2H-acridin-9-one (67).
Following general procedure C, the title compound was prepared to
provide 27% yield as a white crystal, mp = 340ꢀ343 °C. 1H NMR (400
MHz, DMSO) δ 9.93 (s, 1H), 7.83 (d, J = 8.2 Hz, 1H), 7.06 (d, J = 8.2
Hz, 1H), 3.32 (d, J = 0.9 Hz, 3H), 2.78 (t, J = 5.9 Hz, 2H), 2.42 (t, J = 5.5
Hz, 2H), 2.39 (s, 2H), 2.36 (s, 2H), 1.72 (dd, J = 23.8, 5.9 Hz, 4H). 13C
NMR (101 MHz, DMSO) δ 176.21, 146.99, 138.82, 138.00, 124.46,
122.77, 122.05, 121.91, 114.99, 27.33, 21.84, 21.66, 21.63, 20.39, 12.94.
HRMS (ESI) calcd for C15H17NONa [M þ Na]þ, 250.1202; found,
250.1195.
7-Isopropyl-1,2,3,4-tetrahydroacridin-9(10H)-one (61).
Following general procedure C, the title compound was prepared to
provide 11% yield as a tan powder, mp = 275ꢀ277 °C. 1H NMR (400
MHz, DMSO) δ 11.24 (s, 1H), 7.88 (s, 1H), 7.48 (d, J = 7.9 Hz, 1H),
7.39 (d, J = 8.0 Hz, 1H), 2.96 (d, J = 6.0 Hz, 1H), 2.68 (s, 2H), 2.43 (s,
2H), 1.72 (d, J = 19.1 Hz, 4H), 1.23 (d, J = 5.9 Hz, 6H). 13C NMR (101
MHz, DMSO) δ 176.54, 147.00, 142.62, 138.31, 130.68, 123.74, 121.75,
118.06, 115.81, 33.69, 27.76, 24.59, 22.61, 22.40, 22.21. HRMS (ESI)
calcd for C16H20NO [M þ H]þ, 242.1539; found, 242.1540.
6,7-Dimethyl-1,3,4,10-tetrahydro-2H-acridin-9-one (68).
Following general procedure C, the title compound was prepared to
provide 34% yield as a white powder. 1H NMR (400 MHz, DMSO) δ
11.13 (s, 1H), 7.78 (s, 1H), 7.20 (s, 1H), 2.66 (s, 2H), 2.41 (s, 2H), 2.29
(d, J = 9.1 Hz, 6H), 1.75ꢀ1.67 (m, 4H). 13C NMR (101 MHz, DMSO)
δ 146.69, 141.04, 138.51, 131.36, 125.19, 122.28, 117.82, 115.62, 27.77,
22.64, 22.38, 22.23, 20.57, 19.86. HRMS (ESI) calcd for C15H18NO [M
þ H]þ, 228.1383; found, 228.1379.
5,8-Dimethoxy-1,3,4,10-tetrahydro-2H-acridin-9-one (69).
Following general procedure C, the title compound was prepared to
7-Ethoxy-1,2,3,4-tetrahydroacridin-9(10H)-one (62). Fol-
lowing general procedure C, the title compound was prepared to provide
51% yield as a yellow powder, mp = 291ꢀ292 °C. 1H NMR (400 MHz,
DMSO) δ 11.28 (s, 1H), 7.42 (dd, J = 11.0, 5.8 Hz, 2H), 7.19 (dd, J = 8.9,
2.8 Hz, 1H), 4.05 (q, J = 6.9 Hz, 2H), 2.68 (t, J = 5.7 Hz, 2H), 2.43 (d, J =
5.5 Hz, 2H), 1.75ꢀ1.63 (m, 4H), 1.35 (t, J = 6.9 Hz, 3H). 13C NMR (101
MHz, DMSO) δ 175.93, 154.57, 146.51, 134.56, 124.69, 122.41, 119.72,
115.13, 105.38, 63.87, 27.74, 22.65, 22.49, 22.24, 15.29. HRMS (ESI)
calcd for C15H18NO2 [M þ H]þ, 244.1332; found, 244.1323.
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provide 84% yield as a yellow-green powder, mp = 215ꢀ219 °C. H
NMR (400 MHz, DMSO) δ 10.25 (s, 1H), 7.03 (d, J = 8.6 Hz, 1H), 6.55
(d, J = 8.6 Hz, 1H), 3.89 (s, 3H), 3.71 (s, 3H), 2.70 (s, 2H), 2.34 (s, 2H),
1.66 (br d, 4H). 13C NMR (101 MHz, DMSO) δ 175.66, 152.65, 144.61,
141.47, 132.17, 117.75, 114.67, 110.58, 102.85, 56.16, 26.71, 21.90, 21.47.
HRMS (ESI) calcd for C15H18NO3 [M þ H]þ, 260.1281; found,
260.1272.
5,7-Dimethoxy-1,3,4,10-tetrahydro-2H-acridin-9-one (70).
Following general procedure C, the title compound was prepared to
provide 23% yield as a tan powder, mp = 226ꢀ230 °C. 1H NMR (400
MHz, DMSO) δ 10.67 (s, 1H), 7.04 (s, 1H), 6.79 (s, 1H), 3.95 (s, 3H),
3.80 (s, 3H), 2.74 (t, J = 5.3 Hz, 2H), 2.43 (t, J = 5.3 Hz, 2H), 1.68 (d, J =
3.6 Hz, 4H). 13C NMR (101 MHz, DMSO) δ 174.94, 154.78, 149.16,
145.77, 125.34, 124.31, 115.14, 101.88, 95.19, 56.16, 55.21, 27.04, 21.92,
21.89, 21.54. HRMS (ESI) calcd for C15H18NO3 [M þ H]þ, 260.1281;
found, 260.1283.
6,8-Dimethoxy-1,3,4,10-tetrahydro-2H-acridin-9-one (71).
Following general procedure C, the title compound was prepared to
provide 11% yield as a white powder, mp = 267ꢀ270 °C. 1H NMR (400
MHz, DMSO) δ 10.89 (s, 1H), 6.44 (s, 1H), 6.24 (s, 1H), 3.82 (s, 3H),
3.77 (s, 3H), 2.59 (s, 2H), 2.33 (s, 2H), 1.71 (br d, J = 15.8 Hz, 4H). 13C
NMR (101 MHz, DMSO) δ 175.40, 161.27, 160.78, 143.77, 143.25,
116.56, 109.04, 93.46, 90.60, 55.46, 55.05, 26.49, 21.99, 21.58, 21.45.
HRMS (ESI) calcd for C15H18NO3 [M þ H]þ, 260.1281; found,
260.1273.
5,6-Dimethoxy-1,3,4,10-tetrahydro-2H-acridin-9-one (72).
Following general procedure C, the title compound was prepared to
provide 35% yield as a light yellow powder, mp = 206ꢀ207 °C. 1H NMR
(400 MHz, DMSO) δ 10.59 (s, 1H), 7.82 (d, J = 9.0 Hz, 1H), 7.10 (d, J =
9.0 Hz, 1H), 3.95 (s, 3H), 3.87 (s, 3H), 2.79 (s, 2H), 2.44 (s, 2H), 1.73
(br d, J = 14.5 Hz, 4H). 13C NMR (101 MHz, DMSO) δ 175.70, 152.76,
147.14, 134.98, 134.04, 120.67, 118.58, 114.75, 108.68, 60.57, 56.08,
27.22, 21.84, 21.67, 21.53. HRMS (ESI) calcd for C15H18NO3 [M þ
H]þ, 260.1281; found, 260.1280.
9-Oxo-5,6,7,8,9,10-hexahydroacridine-2-carboxylic Acid
Ethyl Ester (63). Following general procedure C, the title compound
was prepared to provide 32% yield as an off-white crystal, mp =
325ꢀ326 °C. 1H NMR (400 MHz, DMSO) δ 11.60 (s, 1H), 8.68 (d,
J = 1.3 Hz, 1H), 8.06 (dd, J = 8.6, 1.5 Hz, 1H), 7.52 (d, J = 8.7 Hz, 1H),
4.33 (q, J = 7.0 Hz, 2H), 2.69 (d, J = 5.9 Hz, 2H), 2.42 (d, J = 5.4 Hz, 2H),
1.73 (dd, J = 25.3, 4.9 Hz, 4H), 1.34 (t, J = 7.0 Hz, 3H). 13C NMR (101
MHz, DMSO) δ 176.57, 166.08, 148.25, 142.67, 131.42, 128.12, 123.83,
122.98, 118.58, 117.55, 61.31, 27.77, 22.31, 22.25, 22.02, 14.90. HRMS
(ESI) calcd C16H18NO3 [M þ H]þ, 272.1281; found, 272.1275.
5,8-Dimethyl-1,3,4,10-tetrahydro-2H-acridin-9-one (64).
Following general procedure C, the title compound was prepared to
provide 74% yield as a yellow crystal, mp = 246ꢀ248 °C. 1H NMR (400
MHz, DMSO) δ 9.66 (s, 1H), 7.20 (d, J = 7.3 Hz, 1H), 6.80 (d, J = 7.3
Hz, 1H), 2.74 (br m, 5H), 2.41 (s, 3H), 2.37 (t, J = 5.9 Hz, 2H), 1.69 (br
m, 4H). 13C NMR (101 MHz, DMSO) δ 178.77, 145.46, 139.30,
136.53, 130.96, 124.10, 122.78, 121.68, 116.94, 26.92, 23.49, 21.93,
21.81, 21.57, 17.56. HRMS (ESI) calcd C15H18NO [M þ H]þ,
228.1383; found, 228.1376.
5,7-Dimethyl-1,3,4,10-tetrahydro-2H-acridin-9-one (65).
Following general procedure C, the title compound was prepared to
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provide 78% yield as an off-white crystal, mp = 323ꢀ326 °C. H NMR
(400 MHz, DMSO) δ 10.97 (s, 1H), 7.06 (s, 1H), 6.74 (s, 1H), 2.79 (s,
3H), 2.64 (s, 2H), 2.38 (s, 2H), 2.34 (s, 3H), 1.72 (br d, J = 15.4 Hz, 4H).
13C NMR (101 MHz, DMSO) δ 178.28, 144.84, 141.08, 139.66, 138.73,
126.06, 119.63, 116.40, 114.83, 26.72, 23.18, 22.04, 21.74, 21.52, 21.01.
HRMS (ESI) calcd for C15H18NO [M þ H]þ, 228.1383; found, 228.1377.
6,8-Dimethyl-1,3,4,10-tetrahydro-2H-acridin-9-one (66).
Following general procedure C, the title compound was prepared to
6,7-Dimethoxy-1,2,3,4-tetrahydroacridin-9(10H)-one (73).
Following general procedures A and B, the title compound was prepared
to provide 40% yield as a yellow powder, mp = 252ꢀ254 °C. 1H NMR
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dx.doi.org/10.1021/jm200015a |J. Med. Chem. 2011, 54, 4399–4426