R. R. Castillo, C. Burgos, J. J. Vaquero, J. Alvarez-Builla
FULL PAPER
1102 cm–1. 1H NMR (300 MHz, CD3OD): δ = 7.96 (td, J = 8.2,
256.0979. C15H14BrNO3 (335.0157): calcd. C 53.59, H 4.20, N 4.17;
2.1 Hz, 1 H), 8.11 (app. t, J = 6.8 Hz, 1 H), 8.43 (m, 2 H), 8.57 found C 53.29, H 4.47, N 4.01.
(dd, J = 9.1, 5.6 Hz, 1 H), 8.82 (dd, J = 10.3, 2.1 Hz, 1 H, dd, 1
7-Hydroxy-9,10-dimethoxy-2-phenylpyrido[2,1-a]isoquinolinylium
Bromide (1q): Bright yellow solid (181 mg, 44%), m.p. Ͼ 265 °C
H), 9.29 (m, 2 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 112.1
(d, JC,F = 26.0 Hz, 1 C), 113.9, 123.7 (d, JC,F = 24.8 Hz, 1 C),
2
2
(dec.) (2-propanol). IR (KBr): ν = 3435, 3063, 2818, 1644, 1608,
˜
3
3
124.5, 125.8, 126.0, 127.3 (d, JC,F = 10.2 Hz, 1 C), 129.1 (d, JC,F
1
1525, 1470, 1424, 1265, 1213 cm–1. H NMR (300 MHz, CD3OD):
4
= 9.9 Hz, 1 C), 137.7, 138.7, 139.8 (d, JC,F = 4.7 Hz, 1 C), 151.7,
δ = 4.12 (s, 3 H, OMe), 4.21 (s, 3 H, OMe), 7.66 (m, 3 H), 7.79 (s,
1 H), 8.14 (dd, JH,H = 7.6, 1.5 Hz, 2 H), 8.22 (dd, JH,H = 7.0,
1
165.3 (d, JC,F = 250.7 Hz, 1 C) ppm. MS (API-ES, Pos): m/z =
214.0 [C13H9FNO]+, [M]+. C13H9BrFNO (292.9852): calcd. C
53.09, H 3.08, N 4.76; found C 52.81, H 3.12, N 4.77.
3
2.0 Hz, 1 H), 8.28 (s, 1 H), 8.36 (s, 1 H), 9.11 (d, JH,H = 7.0 Hz,
4
1 H), 9.25 (d, JH,H = 1.8 Hz, 1 H) ppm. 13C NMR (75 MHz,
CD3OD): δ = 57.0 (1 C, OMe), 57.4 (1 C, OMe), 103.3, 106.6,
112.6, 119.7, 122.2, 125.2, 127.5, 129.0, 130.1, 130.7, 131.9, 136.8,
137.8, 148.2, 150.8, 154.5, 156.6 ppm. HRMS (ESI-TOF, MeOH):
calcd. for [C21H18NO3]+ 332.1287; found 332.1269. C21H18BrNO3
(411.0470): calcd. C 61.18, H 4.40, N 3.40; found C 61.41, H 4.46,
N 3.33.
10-Fluoro-7-hydroxy-4-methylpyrido[2,1-a]isoquinolinylium Bromide
(1m): Pale brown solid (90 mg, 29%), m.p. Ͼ 300 °C (acetonitrile/
toluene). IR (KBr): ν = 2875, 1644, 1614, 1483, 1334, 1086,
˜
804 cm–1. 1H NMR (300 MHz, CD3OD): δ = 3.10 (s, 3 H, Me),
7.99 (td, J = 8.9, 2.3 Hz, 1 H), 8.13 (d, J = 7.6 Hz, 1 H), 8.27 (s, 1
H), 8.36 (app. t, J = 8.2 Hz, 1 H), 8.62 (dd, J = 8.9, 5.6 Hz, 1 H),
8.88 (dd, J = 10.2, 2.3 Hz, 1 H), 9.27 (d, J = 8.6 Hz, 1 H) ppm.
13C NMR (75 MHz, CD3OD): δ = 21.6 (1 C, Me), 109.3, 112.2 (d,
2JC,F = 26.1 Hz, 1 C), 122.9, 123.0, 123.6 (d, 2JC,F = 23.6 Hz, 1 C),
7-Hydroxy-9,10-dimethoxy-2-trifluoromethylpyrido[2,1-a]isoquinol-
inylium Bromide (1r): Pale brown solid (190 mg, 47 %), m.p. Ͼ
241 °C (dec.) (2-propanol). IR (KBr): ν = 3338, 3029, 1618, 1464,
˜
3
125.1, 127.3 (d, 3JC,F = 9.7 Hz), 127.7, 129.9 (d, JC,F = 11.2 Hz, 1
1
1308, 1177 cm–1. H NMR (300 MHz, CD3OD): δ = 4.16 (s, 3 H,
C), 136.9, 146.7, 152.0, 165.5 (d, 1JC,F = 251.5 Hz) ppm. MS (API-
3
OMe), 4.23 (s, 3 H, OMe), 7.86 (s, 1 H), 8.13 (dd, JH,H = 7.0,
ES, Pos): m/z
=
228.1 [C14H11FNO]+, [M]+. C14H11BrFNO
3
1.3 Hz, 1 H), 8.41 (s, 1 H), 8.51 (s, 1 H), 9.33 (d, JH,H = 7.0 Hz,
1 H), 9.53 (br. s, 1 H) ppm. 13C NMR (50 MHz, [D6]DMSO): δ =
(307.0008): calcd. C 54.57, H 3.60, N 4.55; found C 54.27, H 3.66,
N 4.59.
56.0 (1 C, OMe), 56.6 (1 C, OMe), 101.2, 105.3, 112.9, 117.1 (q,
1
3JC,F = 3.1 Hz, 1 C), 120.6, 121.9 (q, JC,F = 273.9 Hz, 1 C, CF3),
4-Ethyl-10-fluoro-7-hydroxypyrido[2,1-a]isoquinolinylium Bromide
(1n): Pale brown solid (84 mg, 26%), m.p. 265–267 °C (acetonitrile/
3
2
123.3, 129.9 (q, JC,F = 3.1 Hz, 1 C), 131.8 (q, JC,F = 35.3 Hz, 1
C), 135.5, 137.5, 150.3, 152.1, 154.3 ppm. MS (API-ES, Pos): m/z
= 324.1 [C16H13F3NO3]+, [M]+. C16H13BrF3NO3 (403.0031): calcd.
C 47.55, H 3.24, N 3.47; found C 47.72, H 3.33, N 3.57.
toluene). IR (KBr): ν = 3357, 2886, 1610, 1481, 1333, 1088,
˜
3
801 cm–1. 1H NMR (300 MHz, CD3OD): δ = 1.63 (t, JH,H
=
3
7.3 Hz, 3 H, Me), 3.45 (q, JH,H = 7.3 Hz, 2 H, CH2), 7.99 (td, J
= 8.6, 2.3 Hz, 1 H), 8.13 (d, J = 7.4 Hz, 1 H), 8.40 (m, 2 H), 8.62
(dd, J = 8.8, 5.6 Hz, 1 H), 8.88 (dd, J = 10.5, 2.4 Hz, 1 H), 9.27
(d, J = 8.5 Hz, 1 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 9.7
(1 C, CH3), 26.5 (1 C, CH2), 107.3, 110.7 (d, 2JC,F = 25.3 Hz, 1 C),
2,7-Dihydroxy-9,10-dimethoxypyrido[2,1-a]isoquinolinylium Bro-
mide (1s): Brown solid (152 mg, 43%), m.p. Ͼ 268 °C (dec.) (2-
propanol). IR (KBr): ν = 3391, 2971, 1647, 1610, 1477, 1284, 1246,
˜
1
1214, 1178 cm–1. H NMR (300 MHz, CD3OD): δ = 4.09 (s, 3 H,
2
3
121.3, 122.0 (d, JC,F = 24.6 Hz, 1 C), 123.5, 124.1, 125.6 (d, JC,F
OMe), 4.12 (s, 3 H, OMe), 7.39 (dd, JH,H = 7.5, 2.4 Hz, 1 H), 7.68
= 10.0 Hz, 1 C), 128.4 (d, 3JC,F = 9.9 Hz, 1 C), 135.4, 139.0, 149.3,
4
(s, 1 H), 7.92 (s, 1 H), 7.95 (s, 1 H), 8.17 (d, JH,H = 2.4 Hz, 1 H),
1
3
8.86 (d, JH,H = 7.5 Hz, 1 H) ppm. 13C NMR (75 MHz, CD3OD):
150.4, 163.8 (d, JC,F = 251.3 Hz, 1 C) ppm. MS (API-ES, Pos):
m/z = 242.2 [C15H13FNO]+, [M]+. C15H13BrFNO (321.0165): calcd.
δ = 56.9 (1 C, OMe), 57.1 (1 C, OMe), 103.4, 106.2, 106.3, 111.5,
115.2, 120.3, 124.6, 140.0, 141.9, 148.1, 153.6, 156.1, 165.2 ppm.
MS (API-ES, Pos): m/z = 272.3 [C15H14NO4]+, [M]+. C15H14BrNO4
(351.0106): calcd. C 51.16, H 4.01, N 3.98; found C 51.09, H 3.95,
N 4.13.
C 55.92, H 4.07, N 4.35; found C 56.10, H 4.02, N 4.49.
10-Fluoro-7-hydroxy-1,3-dimethylpyrido[2,1-a]isoquinolinylium Bro-
mide (1o): Pale brown solid (113 mg, 35%), m.p. Ͼ 300 °C (acetoni-
trile/toluene). IR (KBr): ν = 3414, 2841, 2543, 1653, 1610, 1481,
˜
1431, 1261, 1203, 860 cm–1. 1H NMR (300 MHz, CD3OD): δ =
2.65 (s, 3 H), 3.24 (s, 3 H), 7.94 (td, J = 8.4, 2.4 Hz, 1 H), 8.24 (br.
s, 1 H), 8.29 (s, 1 H), 8.62 (dd, J = 9.1, 6.1 Hz, 1 H), 8.79 (dd, J =
11.7, 2.0 Hz, 1 H), 9.11 (br. s, 1 H) ppm. 13C NMR (75 MHz,
CD3OD): δ = 16.6 (1 C, Me), 24.4 (1 C, Me), 112.9, 114.2 (d, 2JC,F
7-Hydroxy-9,10-dimethoxy-1,3-dimethylpyrido[2,1-a]isoquinolin-
ylium Bromide (1t): Pale yellow solid (153 mg, 42%), m.p. Ͼ 260 °C
(dec.) (2-propanol). IR (KBr): ν = 3435, 3002, 1532, 1479, 1433,
˜
1287, 1203, 1169, 858 cm–1. 1H NMR (300 MHz, CD3OD): δ =
2.60 (s, 3 H, Me), 3.26 (s, 3 H, Me), 4.13 (s, 3 H, OMe), 4.14 (s, 3
H, OMe), 7.86 (s, 1 H), 8.06 (br. s, 1 H), 8.22 (s, 1 H), 8.39 (s, 1
H), 8.92 (br. s, 1 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 17.8
(1 C, Me), 26.0 (1 C, Me), 56.9 (2 C, 2OMe), 103.3, 110.3, 113.7,
122.9, 125.7, 134.0, 135.4, 135.5, 135.9, 142.1, 150.6, 152.9,
155.1 ppm. HRMS (ESI-TOF, MeOH): calcd. for [C17H18NO3]+
284.1287; found 284.1304. C17H18BrNO3 (363.0470): calcd. C
56.06, H 4.98, N 3.85; found C 55.90, H 4.99, N 3.80.
2
= 26.8 Hz, 1 C), 120.8 (d, JC,F = 24.2 Hz, 1 C), 125.0, 125.5 (d,
3
3JC,F = 9.8 Hz, 1 C), 128.4 (d, JC,F = 10.0 Hz, 1 C), 134.9, 135.5,
1
136.2, 142.1, 142.2, 149.7, 162.8 (d, JC,F = 249.9 Hz, 1 C) ppm.
MS (API-ES, Pos): m/z
=
242.2 [C15H13FNO]+, [M]+.
C15H13BrFNO (321.0165): calcd. C 55.92, H 4.07, N 4.35; found
C 56.27, H 3.96, N 4.60.
7-Hydroxy-9,10-dimethoxypyrido[2,1-a]isoquinolinylium
Bromide
(1p): Pale brown solid (148 mg, 44%), m.p. Ͼ 254 °C (dec.) (2- 7-Hydroxy-9,10-dimethoxy-1,3,4-trimethylpyrido[2,1-a]isoquinol-
propanol). IR (KBr): ν = 3577, 3449, 2943, 1624, 1500, 1474, 1297, inylium Bromide (1u): Pale yellow solid (178 mg, 47%), m.p. Ͼ
˜
1264, 1218, 1183 cm–1. H NMR (300 MHz, CD3OD): δ = 4.13 (s, 270 °C (dec.) (2-propanol). IR (KBr): ν = 3435, 3118, 2769, 2578,
1
˜
3
1
3 H, OMe), 4.17 (s, 3 H, OMe), 7.78 (s, 1 H), 7.90 (app. t, JH,H
=
1640, 1488, 1288, 1211 cm–1. H NMR (300 MHz, [D6]DMSO): δ
3
6.8 Hz, 1 H), 8.25 (m, 3 H), 9.10 (d, JH,H = 6.6 Hz, 1 H), 9.18 (d,
3JH,H = 8.9 Hz, 1 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 55.6
(1 C, OMe), 55.9 (1 C, OMe), 101.7, 104.7, 111.7, 120.5, 122.2,
122.4, 123.6, 134.5, 136.2, 137.6, 149.8, 153.1, 155.2 ppm. HRMS
(ESI-TOF, MeOH): calcd. for [C15H14NO3]+ 256.0974; found
= 2.60 (s, 3 H, Me), 2.82 (s, 3 H, Me), 3.16 (s, 3 H, Me), 4.05 (s, 3
H, OMe), 4.06 (s, 3 H, OMe), 7.71 (br. s, 1 H), 8.15 (br. s, 1 H),
8.27 (m, 2 H) ppm. 13C NMR (50 MHz, [D6]DMSO): δ = 17.1 (1
C, Me), 19.1 (1 C, Me), 24.6 (1 C, Me), 55.6 (1 C, OMe), 55.7 (1
C, OMe), 100.9, 108.5, 109.2, 120.8, 122.0, 130.7, 131.2, 136.0,
626
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Eur. J. Org. Chem. 2011, 619–628