UPDATES
7.34–7.24 (m, 1H), 7.19 (d, J=2.2 Hz, 1H), 7.10 (dd, J=8.1,
2.3 Hz, 1H), 4.84 (s, 2H), 2.50 (s, 3H); 13C NMR (75 MHz,
chloroform-d): d=136.15, 131.46, 130.92, 128.63, 126.77 (d,
J=2.6 Hz), 125.15, 118.13, 113.44, 19.76; GC-MS (EI,
70 eV): m/z (%)=235 (M+, 100), 236 (16), 234 (80), 219
(35), 132 (52), 131 (29), 116 (15), 105 (13), 104 (92), 103
(16), 89 (36), 77 (53), 76 (11), 63 (11), 51 (21), 32 (11).
3-(3-Methoxyphenyl)isoquinolin-1-amine
(3t):
yield:
137 mg (55%); light yellow solid; 1H NMR (300 MHz,
chloroform-d): d=7.83–7.73 (m, 2H), 7.71–7.56 (m, 3H),
7.48 (dd, J=5.2, 1.0 Hz, 1H), 7.46–7.33 (m, 2H), 6.95 (ddd,
J=8.2, 2.6, 1.0 Hz, 1H), 5.34 (s, 2H), 3.90 (s, 3H); 13C NMR
(75 MHz, chloroform-d): d=159.98, 155.96, 149.39, 141.48,
138.22, 130.29, 129.59, 127.61, 126.01, 122.64, 119.31, 117.08,
114.24, 112.14, 109.07, 55.40; GC-MS (EI, 70 eV): m/z
(%)=250 (M+, 100), 251 (18), 249 (77), 221 (13), 220 (36),
219 (27), 205 (11), 204 (12), 190 (11), 220 (36), 219 (27), 205
(11).
3-(2-Chlorophenyl)isoquinolin-1-amine
(3m):
yield:
117 mg (46%); light yellow solid; 1H NMR (300 MHz,
chloroform-d): d=7.82 (dd, J=8.3, 1.0 Hz, 1H), 7.78–7.74
(m, 1H), 7.68–7.60 (m, 2H), 7.56–7.45 (m, 2H), 7.41–7.27
(m, 3H), 5.34 (s, 2H); 13C NMR (75 MHz, chloroform-d):
d=155.72, 148.61, 139.63, 137.42, 132.40, 131.49, 130.29,
130.04, 128.91, 127.50, 126.75, 126.32, 122.50, 116.74, 113.15;
GC-MS (EI, 70 eV): m/z (%)=254 (M+, 100), 266 (30), 265
(18), 220 (18), 219 (63), 218 (21), 190 (14).
3-[4-(Methylthio)phenyl]isoquinolin-1-amine (3u): yield:
192 mg (72%); light yellow solid; 1H NMR (300 MHz,
chloroform-d): d=8.08–7.91 (m, 2H), 7.82–7.69 (m, 2H),
7.59 (ddd, J=8.1, 6.9, 1.2 Hz, 1H), 7.49–7.38 (m, 2H), 7.38–
7.29 (m, 2H), 5.32 (s, 2H), 2.53 (s, 1H); 13C NMR (75 MHz,
chloroform-d): d=155.86, 148.79, 138.52, 138.15, 136.57,
130.20, 127.41, 127.07, 126.46, 125.77, 122.55, 116.84, 108.24,
15.72.
3-(3-Chlorophenyl)isoquinolin-1-amine
(3n):
yield:
137 mg (54%); light yellow solid; 1H NMR (300 MHz,
chloroform-d): d=8.18–8.04 (m, 1H), 7.93 (dt, J=7.3,
1.7 Hz, 1H), 7.83–7.72 (m, 2H), 7.63 (ddd, J=8.1, 6.9,
1.2 Hz, 1H), 7.54–7.44 (m, 2H), 7.44–7.28 (m, 2H), 5.28 (s,
2H); 13C NMR (75 MHz, chloroform-d): d=155.90, 147.95,
141.65, 138.04, 134.58, 130.38, 129.72, 128.08, 127.62, 126.95,
126.27, 124.75, 122.55, 117.16, 109.12; GC-MS (EI, 70 eV):
m/z (%)=254 (M+, 100), 256 (34), 255 (21), 253 (10), 218
(18).
3-(Naphthalen-2-yl)isoquinolin-1-amine
(3v):
yield:
127 mg (47%); light yellow solid; 1H NMR (300 MHz,
chloroform-d): d=8.60 (d, J=1.7 Hz, 1H), 8.19 (dd, J=8.6,
1.8 Hz, 1H), 8.01–7.76 (m, 5H), 7.70–7.58 (m, 2H), 7.48
(ddd, J=9.7, 6.1, 1.6 Hz, 3H), 5.34 (s, 2H); 13C NMR
(75 MHz, chloroform-d): d=155.92, 149.20, 138.26, 136.97,
133.64, 133.36, 130.36, 128.65, 128.13, 127.60, 126.05 (d, J=
3.1 Hz), 125.97, 124.68, 122.62, 117.04, 109.28; GC-MS (EI,
70 eV): m/z (%)=270 (M+, 100), 271 (23), 269 (27).
3-(4-Chlorophenyl)isoquinolin-1-amine
(3o):
yield:
130 mg (51%); light yellow solid; 1H NMR (300 MHz,
chloroform-d): d=8.06–7.95 (m, 2H), 7.85–7.73 (m, 2H),
7.63 (ddd, J=8.2, 6.9, 1.2 Hz, 1H), 7.55–7.38 (m, 4H), 5.30
(s, 2H); 13C NMR (75 MHz, chloroform-d): d=155.86,
148.08, 138.09, 134.15, 130.47, 128.69, 128.02, 127.58, 126.20,
122.59, 116.99, 108.79; GC-MS (EI, 70 eV): m/z (%)=254
(M+, 100), 256 (33), 255 (20), 253 (11), 218 (20).
3-(Pyridin-4-yl)isoquinolin-1-amine (3w): yield: 119 mg
1
(54%); light yellow solid; H NMR (300 MHz, chloroform-
d): d=8.85–8.57 (m, 2H), 8.08–7.89 (m, 2H), 7.90–7.75 (m,
2H), 7.66 (ddd, J=8.1, 6.9, 1.2 Hz, 1H), 7.61–7.42 (m, 2H),
5.41 (s, 2H); 13C NMR (75 MHz, chloroform-d): d=156.20,
149.93, 147.04, 146.35, 137.71, 130.59, 127.83, 126.94, 122.64,
121.00, 117.78, 110.00; GC-MS (EI, 70 eV): m/z (%)=221
(M+, 100), 222 (16), 220 (30), 193 (10).
3-(p-Tolyl)isoquinolin-1-amine (3q): yield: 133 mg (57%);
light yellow solid; 1H NMR (300 MHz, chloroform-d): d=
8.10–7.91 (m, 2H), 7.85–7.69 (m, 2H), 7.60 (ddd, J=8.1, 6.9,
1.2 Hz, 1H), 7.51–7.35 (m, 2H), 7.35–7.20 (m, 2H), 5.28 (s,
2H), 2.42 (s, 3H); 13C NMR (75 MHz, chloroform-d): d=
155.81, 149.56, 138.23, 137.99, 137.01, 130.11, 129.25, 127.41,
126.62, 125.64, 122.53, 116.78, 108.34, 21.24; GC-MS (EI,
70 eV): m/z (%)=234 (M+, 100), 235 (15).
3-(o-Tolyl)isoquinolin-1-amine (3r): yield: 190 mg (81%);
light yellow solid; 1H NMR (300 MHz, chloroform-d): d=
7.89–7.78 (m, 1H), 7.73 (ddt, J=8.3, 1.1, 0.5 Hz, 1H), 7.63
(ddd, J=8.1, 6.9, 1.2 Hz, 1H), 7.58–7.40 (m, 2H), 7.33–7.27
(m, 3H), 7.12 (d, J=0.9 Hz, 1H), 5.38 (s, 2H), 2.42 (s, 3H);
13C NMR (75 MHz, chloroform-d): d=155.46, 151.86,
140.77, 137.79, 135.96, 130.54, 130.20, 129.57, 127.78, 127.25,
125.88, 125.69, 122.54, 116.36, 112.08, 20.39; GC-MS (EI,
70 eV): m/z (%)=233 (M+, 100), 234 (53), 216 (20), 116
(18).
3-(Pyridin-3-yl)isoquinolin-1-amine (3x): yield: 108 mg
1
(49%); light yellow solid; H NMR (300 MHz, chloroform-
d): d=9.77–8.95 (m, 1H), 8.60 (dd, J=4.8, 1.7 Hz, 1H), 8.36
(dt, J=8.0, 2.0 Hz, 1H), 7.98–7.72 (m, 2H), 7.65 (ddd, J=
8.2, 6.9, 1.1 Hz, 1H), 7.55–7.44 (m, 2H), 7.41–7.31 (m, 1H),
5.34 (s, 2H); 13C NMR (75 MHz, chloroform-d): d=156.22,
149.10, 148.28, 146.74, 138.01, 135.33, 134.19, 130.57, 127.67,
126.51, 123.45, 122.66, 117.25, 109.26; GC-MS (EI, 70 eV):
m/z (%)=221 (M+, 100), 222 (16), 220 (30), 193 (10).
Acknowledgements
The authors thank the funding support from the Innovative
Medicines Initiative Joint Undertaking (CHEM21) under
grant agreement no. 115360, resources of which are com-
posed of a financial contribution from the European Unionꢀs
Seventh Framework Programme (FP7/2007–2013) and
EFPIA companies in kind contribution. We also thank the
staff in the analytical department of LIKAT for their excel-
lent analytical support. The generous support from Prof.
Matthias Beller is appreciated. We also wish to that the kind
help from Chaoren Shen (LIKAT), Dr. Pamela Alsabeh
(LIKAT), Prof. Scott G. Stewart (The University of Western
Australia) and Prof. Michael Willis (University of Oxford,
U.K.) for their English polishing.
3-(4-Methoxyphenyl)isoquinolin-1-amine
(3s):
yield:
200 mg (80%); light yellow solid; 1H NMR (300 MHz,
chloroform-d): d=8.11–7.97 (m, 2H), 7.82–7.68 (m, 2H),
7.59 (ddd, J=8.2, 6.9, 1.2 Hz, 1H), 7.50–7.37 (m, 2H), 7.08–
6.87 (m, 2H), 5.25 (s, 2H), 3.87 (s, 3H); 13C NMR (75 MHz,
chloroform-d): d=159.81, 155.77, 149.25, 138.31, 132.48,
130.12, 127.97, 127.33, 125.48, 122.54, 116.57, 113.91, 107.76,
55.31; GC-MS (EI, 70 eV): m/z (%)=250 (M+, 100), 251
(16), 235 (25), 207 (23).
Adv. Synth. Catal. 0000, 000, 0 – 0
6
ꢃ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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