Microwave-Assisted Synthesis of β-Carbolines and Congeners
0.979 mmol scale in 10 mL of ACN provided the 1ah as a crystal-
line solid (259 mg, 99%). 1H NMR (500 MHz, [D6]DMSO): δ =
1.69–1.73 (overlapping doublets, J = 6.6, 6.9 Hz, 3 H), 3.01–3.12
(m, 1 H), 3.30–3.33 (m, 1 H), 4.46–4.61 (m, 1 H), 7.73–7.81 (m, 1
H), 7.03 (m, 1 H), 7.12 (t, J = 7.4 Hz, 1 H), 7.36 (m, 1 H), 7.49 (d,
J = 7.6 Hz, 1 H), 9.97 (br. s, 2 H), 11.30–11.36 (overlapping singlets,
1 H) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 16.4, 17.8,
21.7, 22.2, 47.2, 49.5, 51.0, 54.8, 103.6, 104.6, 111.4, 118.0, 119.1,
121.7, 125.6, 130.9, 136.4, 170.0 ppm.
1-Isopropyl-6-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
TFA Salt (1an):[27] Employing General Method A on a 0.158 mmol
scale in 2 mL of DCE provided 1an as an olive green crystalline
solid (51 mg, 90%); m.p. 141–142 °C. 1H NMR (300 MHz, [D6]-
DMSO): δ = 0.88 (d, J = 6.9 Hz, 3 H), 1.13 (d, J = 6.9 Hz, 3 H),
2.55 (m, 1 H), 2.90 (m, 2 H), 3.31 (m, 1 H), 3.58 (m, 1 H), 3.76 (s,
3 H), 4.62 (m, 1 H), 6.67 (dd, J = 8.8, 2.5 Hz, 1 H), 6.97 (d, J =
2.5 Hz, 1 H), 7.26 (d, J = 8.5 Hz, 1 H), 8.34 (br. s, 1 H), 9.35 (br.
s, 1 H), 10.85 (s, 1 H) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ
= 16.7, 19.3, 19.7, 44.0, 56.5, 60.7, 101.4, 108.2, 113.2, 113.8, 127.9,
130.1, 133.7, 155.8 ppm.
(3S)-Methyl 1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-
carboxylate HCl Salt (1ai):[26] Employing General Method C on a
0.393 mmol scale in 5 mL of ACN provided 1ai as a crystalline
solid (90 mg, 82%). 1H NMR (500 MHz, [D6]DMSO): δ = 1.73 (d,
J = 6.6 Hz, 3 H), 3.06 (m, 1 H), 3.31 (m, 1 H), 3.88 (s, 3 H), 4.65
(m, 1 H), 4.77 (m, 1 H), 7.04 (t, J = 7.4 Hz, 1 H), 7.14 (t, J =
7.4 Hz, 1 H), 7.38 (d, J = 7.9 Hz, 1 H), 7.50 (d, J = 7.9 Hz, 1 H),
9.91 (br. s, 1 H) 10.27 (br. s, 1 H), 11.29 (s, 1 H) ppm. 13C NMR
(125.7 MHz, [D6]DMSO): δ = 17.2, 23.0, 50.4, 53.8, 55.3, 105.0,
112.1, 118.9, 120.0, 122.6, 126.3, 131.6, 137.1, 169.7 ppm.
1-Isopropyl-7-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
HCl Salt (1ao):[27] Employing General Method B on a 0.316 mmol
scale in 3 mL of DCE provided 1ao as a crystalline solid (73 mg,
1
82%). H NMR (500 MHz, [D6]DMSO): δ = 0.89 (d, J = 6.9 Hz,
3 H), 1.13 (d, J = 6.9 Hz, 3 H), 2.89 (m, 2 H), 3.31 (m, 2 H), 3.56
(m, 1 H), 3.77 (s, 3 H), 4.59 (m, 1 H), 6.69 (dd, J = 8.5, 2.2 Hz, 1
H), 6.87 (d, J = 2.2 Hz, 1 H), 7.34 (d, J = 8.5 Hz, 1 H), 8.31 (br.
s, 1 H), 9.32 (br. s, 1 H), 10.82 (s, 1 H) ppm. 13C NMR (125.7 MHz,
[D6]DMSO): δ = 16.4, 16.5, 16.6, 29.2, 41.7, 55.1, 57.8, 94.7, 106.5,
108.9, 118.6, 120.1, 127.6, 137.2, 155.9 ppm.
1-Ethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole TFA Salt (1aj):[25]
Employing General Method A on a 0.624 mmol scale in 5 mL of
1-Propyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole TFA Salt
(1ap):[28] Employing General Method A on a 0.624 mmol scale in
3 mL of DCE provided 1ap as a crystalline solid (152 mg, 74%).
1H NMR (500 MHz, [D6]DMSO): δ = 0.99 (t, J = 7.3 Hz, 3 H),
1.54 (m, 2 H), 1.86 (m, 1 H), 2.12 (m, 1 H), 2.94 (m, 2 H), 3.34
(m, 1 H), 3.59 (m, 1 H), 4.67 (m, 1 H), 7.03 (t, J = 7.6 Hz, 1 H),
7.12 (t, J = 7.6 Hz, 1 H), 7.37 (d, J = 8.2 Hz, 1 H), 7.47 (d, J =
7.6 Hz, 1 H), 8.90 (br. s, 1 H), 9.44 (br. s, 1 H), 11.09 (s, 1 H) ppm.
13C NMR (125.7 MHz, [D6]DMSO): δ = 13.9, 18.2, 18.4, 33.8,
41.2, 52.6, 105.9, 111.6, 118.3, 119.3, 122.0, 126.1, 130.4,
136.5 ppm.
1
DCE provided 1aj as a crystalline solid (192 mg, 98%). H NMR
(500 MHz, [D6]DMSO): δ = 1.08 (t, J = 7.4 Hz, 3 H), 1.91 (m, 1
H), 2.21 (m, 1 H), 2.94 (m, 2 H), 3.34 (m, 1 H), 3.60 (m, 1 H), 4.61
(m, 1 H), 7.03 (t, J = 7.3 Hz, 1 H), 7.12 (t, J = 7.3 Hz, 1 H) 7.37
(d, J = 7.9 Hz, 1 H), 7.47 (d, J = 7.9 Hz, 1 H), 8.97 (br. s, 1 H),
9.55 (br. s, 1 H), 11.12 (s, 1 H) ppm. 13C NMR (125.7 MHz, [D6]-
DMSO): δ = 9.6, 18.3, 24.7, 41.0, 53.9, 105.9, 111.5, 118.1, 119.1,
121.9, 125.9, 130.2, 136.4 ppm.
1-Ethyl-6-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole TFA
Salt (1ak): Employing General Method A on a 0.158 mmol scale
in 2 mL of DCE provided 1ak as a cream colored crystalline solid
(46 mg, 84%); m.p. 219–220 °C. 1H NMR (300 MHz, [D6]DMSO):
δ = 1.07 (t, J = 7.3 Hz, 3 H), 1.89 (m, 1 H), 2.19 (m, 1 H), 2.90
(m, 2 H), 3.31 (m, 1 H), 3.58 (m, 1 H), 3.76 (s, 3 H), 4.58 (m, 1
H), 6.76 (d, J = 8.5 Hz, 1 H), 6.96 (s, 1 H), 7.25 (d, J = 8.8 Hz, 1
H), 8.92 (br. s, 1 H), 9.51 (br. s, 1 H), 10.93 (s, 1 H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 9.6, 18.3, 24.6, 41.01, 53.8, 55.4, 100.1,
105.6, 111.7, 112.1, 126.2, 130.7, 131.3, 153.4 ppm. HRMS (ESI)
m/z calculated for C14H19N2O [M + H]+ 231.1497, found 231.1489.
1-Cyclopropyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole TFA Salt
(1aq): Employing General Method A on a 0.624 mmol scale in
5 mL of DCE provided 1aq as a white crystalline solid (188 mg,
92%); m.p. 244–245 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 0.67
(m, 2 H), 0.85 (m, 2 H), 1.21 (m, 1 H), 2.95 (m, 2 H), 3.31 (m, 1
H), 3.64 (m, 1 H), 3.95 (d, J = 10.1 Hz, 1 H), 7.03 (t, J = 7.3 Hz,
1 H), 7.13 (t, J = 7.3 Hz, 1 H), 7.42 (d, J = 7.9 Hz, 1 H), 7.48 (d,
J = 7.9 Hz, 1 H), 9.24 (br. s, 1 H), 9.36 (br. s, 1 H), 10.96 (s, 1
H) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 2.9, 4.3, 12.6,
18.2, 40.5, 57.3, 105.5, 111.6, 118.0, 119.0, 121.8, 125.7, 129.8,
136.4 ppm. HRMS (ESI) m/z calculated for C14H17N2 [M + H]+
213.1392, found 213.1387.
1-Ethyl-7-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole TFA
Salt (1al):[6] Employing General Method A on a 0.394 mmol scale
in 5 mL of DCE provided 1al as a crystalline solid (95 mg, 70%).
1H NMR (500 MHz, [D6]DMSO): δ = 1.07 (t, J = 7.4 Hz, 3 H),
1.87 (m, 1 H), 2.17 (m, 1 H), 2.89 (m, 2 H), 3.32 (m, 1 H), 3.56
(m, 1 H), 3.77 (s, 3 H), 4.56 (m, 1 H), 6.69 (dd, J = 8.5, 2.2 Hz, 1
H), 6.86 (d, J = 2.2 Hz, 1 H), 7.34 (d, J = 8.8 Hz, 1 H), 8.78 (br.
s, 1 H), 9.36 (br. s, 1 H), 10.88 (s, 1 H) ppm. 13C NMR (125.7 MHz,
[D6]DMSO): δ = 9.5, 18.1, 24.6, 40.8, 53.7, 55.2, 94.7, 105.6, 108.9,
118.6, 120.1, 128.5, 137.1, 155.9 ppm.
1-Cyclopropyl-7-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
TFA Salt (1ar): Employing General Method A on a 0.394 mmol
scale in 5 mL of DCE provided 1ar as a yellow crystalline solid
(110 mg, 79 %); m.p. 216–216 °C. 1H NMR (500 MHz, [D6]-
DMSO): δ = 0.66 (m, 2 H), 0.82 (m, 2 H), 1.19 (m, 1 H), 2.91 (m,
2 H), 3.30 (m, 1 H), 3.60 (m, 1 H), 3.77 (s, 3 H), 3.89 (d, J =
9.8 Hz, 1 H), 6.69 (dd, J = 8.5, 2.2 Hz, 1 H), 6.92 (d, J = 2.2 Hz,
1 H), 7.36 (d, J = 8.5 Hz, 1 H), 9.10–9.40 (br. s, 2 H), 10.76 (s, 1
H) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 2.9, 4.1, 18.2,
40.5, 55.1, 57.3, 94.9, 105.4, 108.8, 118.6, 120.0, 128.4, 137.2,
155.9 ppm. HRMS (ESI) m/z calculated for C15H19N2O [M + H]+
243.1497, found 243.1489.
1-Isopropyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole TFA Salt
(1am):[11] Employing General Method A on a 0.936 mmol scale in
5 mL of DCE provided 1am as a crystalline solid (311 mg, 99%).
1H NMR (500 MHz, [D6]DMSO): δ = 0.89 (d, J = 7.3 Hz, 3 H),
1.15 (d, J = 7.3 Hz, 3 H), 2.60 (m, 1 H), 2.90–2.99 (m, 2 H), 3.32
(m, 1 H), 3.60 (m, 1 H), 4.65 (m, 1 H), 7.03 (t, J = 7.3 Hz, 1 H), 1-(Pyridin-3-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole TFA Salt
7.12 (t, J = 7.3 Hz, 1 H), 7.38 (d, J = 7.9 Hz, 1 H), 7.47 (d, J =
7.9 Hz, 1 H), 8.52 (br. s, 1 H), 9.60 (br. s, 1 H), 11.06 (s, 1 H) ppm.
13C NMR (125.7 MHz, [D6]DMSO): δ = 16.3, 18.5, 18.6, 29.2,
(1as):[29] Utilizing a modification of General Method A, tryptamine
(50 mg, 0.312 mmol, 1 equiv.) was added to an oven-dried micro-
wave vial designed for reaction volumes of 2–5 mL along with DCE
41.8, 57.8, 106.3, 111.32, 117.9, 118.9, 121.7, 125.8, 129.1, (3 mL), followed by 3-pyridinecarbaldehyde (29 μL, 0.312 mmol,
136.4 ppm.
1 equiv.) and TFA (48 μL, 0.624 mmol, 2 equiv.) with stirring. Ad-
Eur. J. Org. Chem. 2014, 1653–1665
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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