PAPER
Novel Hexacyclic Isoquinolinobenzazepinoindoles
1561
1H NMR (300 MHz, CDCl3): δ = 7.84 (s, 1 H), 7.72 (s, 1 H), 7.52
(d, J = 7.5 Hz, 1 H), 7.35 (t, J = 7.9 Hz, 1 H), 7.27–7.23 (m, 1 H),
7.05–7.00 (m, 1 H), 6.98–6.93 (m, 3 H), 6.87–6.78 (m, 5 H), 6.43
(s, 1 H), 6.07 (s, 1 H), 5.47 (s, 1 H), 2.32 (s, 3 H), 1.03 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 162.2, 158.9, 150.4, 143.6, 143.5,
138.0, 137.4, 135.7, 135.1, 131.6, 130.7, 129.4, 128.7, 128.6, 128.3,
128.0, 125.9, 124.6, 124.5, 123.5, 123.3, 120.7, 119.9, 114.8, 114.5,
113.1, 112.8, 110.4, 99.0, 61.3, 34.5, 31.3, 21.3 (extra peaks are
present due to 13C–19F couplings).
9-(Cyclohex-1-en-1-yl)-13-fluoro-14b,16-dihydroindo-
lo[3′,4′:3,4,5]pyrido[2′,3′:6,7]azepino[2,1-a]isoquinoline (3w)
Yield: 0.130 g (65%); yellow solid; mp 135–137 °C; Rf = 0.52
(EtOAc–hexane, 1:4).
IR (KBr): 3534, 2963, 2532, 1526 cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 11.06–11.01 (m, 1 H), 8.66–
8.61 (m, 1 H), 8.17–8.07 (m, 1 H), 7.92–7.90 (m, 1 H), 7.48–7.46
(m, 1 H), 7.33–7.30 (m, 2 H), 7.18–7.15 (m, 1 H), 7.10–7.08 (m, 2
H), 6.51–6.48 (m, 1 H), 6.08–6.04 (m, 2 H), 5.67–5.64 (m, 1 H),
1.82 (s, 2 H), 1.26–1.14 (m, 6 H).
HRMS (ESI): m/z [M + H]+ calcd for C34H30FN2: 485.2393; found:
13C NMR (75 MHz, DMSO-d6): δ = 161.3, 158.2, 146.7, 145.2,
140.9, 137.0, 136.6, 134.7, 133.8, 133.7, 132.2, 129.8, 129.7, 129.5,
128.5, 127.4, 121.9, 121.3, 121.2, 120.0, 114.1, 113.0, 111.9, 97.6,
59.7, 36.5, 24.7, 21.7, 21.2 (extra peaks are present due to 13C–19F
couplings).
HRMS (ESI): m/z [M + H]+ calcd for C28H23FN3: 420.1876; found:
420.1868.
485.2380.
9-(Cyclohex-1-en-1-yl)-13-fluoro-5-methyl-14b,16-dihydroben-
zo[6,7]indolo[3′,4′:3,4,5]azepino[2,1-a]isoquinoline (3t)
Yield: 0.145 g (75%); reddish oil; Rf = 0.59 (EtOAc–hexane, 1:4).
IR (neat): 3502, 2902, 2502, 1580 cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 10.86 (s, 1 H), 7.80 (s, 1 H),
7.41 (d, J = 7.4 Hz, 1 H), 7.31 (d, J = 7.9 Hz, 1 H), 7.23 (d, J = 7.6
Hz, 2 H), 7.00 (d, J = 8.0 Hz, 3 H), 6.94 (d, J = 7.9 Hz, 1 H), 6.36
(s, 1 H), 5.92 (s, 1 H), 5.62 (s, 1 H), 5.25 (s, 1 H), 2.40 (s, 3 H), 2.40
(s, 2 H), 1.98 (s, 3 H), 1.79 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 161.9, 158.7, 146.8, 143.3, 139.4,
137.9, 137.3, 136.0, 135.9, 131.5, 129.4, 129.3, 128.6, 127.9, 125.8,
124.3, 124.2, 123.4, 123.1, 120.6, 119.6, 114.6, 114.3, 114.2, 113.0,
112.7, 110.1, 95.7, 60.5, 27.0, 25.4, 22.8, 22.5, 21.4 (extra peaks are
present due to 13C–19F couplings).
9-[4-(tert-Butyl)phenyl]-13-methoxy-14b,16-dihydroindo-
lo[3′,4′:3,4,5]pyrido[2′,3′:6,7]azepino[2,1-a]isoquinoline (3x)
Yield: 0.140 g (61%); yellow solid; mp 129–133 °C; Rf = 0.48
(EtOAc–hexane, 1:4).
IR (KBr): 3502, 3012, 2205, 1598 cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 11.02 (s, 1 H), 8.46 (s, 1 H),
8.11 (d, J = 6.7 Hz, 1 H), 7.51–7.48 (m, 2 H), 7.40 (s, 1 H), 7.18–
7.10 (m, 2 H), 7.03–7.01 (m, 3 H), 6.90 (s, 2 H), 6.74–6.72 (m, 1 H),
6.56 (s, 1 H), 6.13 (s, 1 H), 5.62 (s, 1 H), 3.79 (s, 3 H), 1.12 (s, 9 H).
HRMS (ESI): m/z [M + H]+ calcd for C30H26FN2: 433.2080; found:
13C NMR (75 MHz, DMSO-d6): δ = 157.2, 149.7, 146.2, 141.8,
140.4, 137.1, 136.4, 134.5, 133.8, 133.6, 132.2, 129.9, 129.7, 129.5,
128.5, 127.3, 124.5, 122.0, 121.8, 121.5, 121.2, 120.2, 113.3, 111.9,
101.8, 60.0, 55.1, 34.0, 30.8.
HRMS (ESI): m/z [M + H]+ calcd for C33H30N3O: 484.2389; found:
484.2384.
433.2072.
9-(Cyclohex-1-en-1-yl)-13-methoxy-5-methyl-14b,16-dihydro-
benzo[6,7]indolo[3′,4′:3,4,5]azepino[2,1-a]isoquinoline (3u)
Yield: 0.132 g (66%); reddish oil; Rf = 0.63 (EtOAc–hexane, 1:4).
IR (neat): 3433, 2969, 2135, 1656 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.96 (s, 1 H), 7.74 (s, 1 H), 7.42
(d, J = 6.9 Hz, 1 H), 7.28 (s, 1 H), 7.22 (d, J = 5.4 Hz, 1 H), 7.00 (s,
2 H), 6.96 (d, J = 8.6 Hz, 1 H), 6.77 (d, J = 8.3 Hz, 1 H), 6.66 (s, 1
H), 6.41 (s, 1 H), 5.95 (s, 1 H), 5.68 (s, 1 H), 5.33 (s, 1 H), 3.77 (s,
3 H), 2.42 (s, 3 H), 2.03–2.00 (m, 5 H), 1.83 (m, 3 H).
9-(Cyclohex-1-en-1-yl)-13-methoxy-14b,16-dihydroindo-
lo[3′,4′:3,4,5]pyrido[2′,3′:6,7]azepino[2,1-a]isoquinoline (3y)
Yield: 0.129 g (63%); reddish oil; Rf = 0.50 (EtOAc–hexane, 1:4).
IR (neat): 3472, 2993, 2522, 1626 cm–1.
13C NMR (75 MHz, CDCl3): δ = 156.9, 145.5, 143.8, 139.4, 137.3,
136.1, 129.4, 129.2, 128.5, 128.0, 127.8, 126.0, 124.2, 123.8, 123.6,
122.9, 120.6, 119.5, 114.2, 113.3, 112.0, 110.0, 96.3, 61.1, 55.6,
27.0, 25.5, 22.6, 21.4.
1H NMR (300 MHz, DMSO-d6): δ = 10.95 (d, J = 1.9 Hz, 1 H),
8.60–8.58 (m, 1 H), 8.07 (d, J = 7.4 Hz, 1 H), 7.46–7.41 (m, 2 H),
7.32–7.26 (m, 2 H), 7.02 (d, J = 8.0 Hz, 1 H), 6.88–6.85 (m, 2 H),
6.47 (s, 1 H), 6.00 (s, 1 H), 5.65 (s, 1 H), 5.42 (s, 1 H), 3.77 (s, 3 H),
1.83 (s, 2 H), 1.27 (s, 6 H).
HRMS (ESI): m/z [M + H]+ calcd for C31H29N2O: 445.2280; found:
13C NMR (75 MHz, DMSO-d6): δ = 156.9, 146.3, 143.5, 141.4,
140.2, 139.0, 134.9, 134.1, 129.9, 128.6, 127.9, 126.1, 124.1, 123.1,
122.6, 121.2, 115.6, 113.2, 111.9, 111.8, 98.6, 59.7, 55.1, 26.5,
24.7, 21.8, 21.3.
445.2267.
13-Fluoro-9-(p-tolyl)-14b,16-dihydroindolo[3′,4′:3,4,5]pyri-
do[2′,3′:6,7]azepino[2,1-a]isoquinoline (3v)
Yield: 0.131 g (64%); yellow solid; mp 130–133 °C; Rf = 0.49
(EtOAc–hexane, 1:4).
HRMS (ESI): m/z [M + H]+ calcd for C29H26N3O: 432.2076; found:
432.2066.
IR (KBr): 3424, 2763, 2522, 1626 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.48 (d, J = 3.1 Hz, 1 H), 8.33 (s,
1 H), 8.17 (d, J = 7.1 Hz, 1 H), 7.69 (d, J = 8.1 Hz, 1 H), 7.53 (s, 4
H), 7.49 (s, 6 H), 6.22 (s, 1 H), 6.01 (s, 1 H), 5.56 (s, 1 H), 2.39 (s,
3 H).
13C NMR (100 MHz, DMSO-d6): δ = 161.3, 159.1, 155.4, 152.6,
147.6, 147.5, 146.6, 141.3, 140.5, 138.6, 138.1, 137.8, 133.9, 133.7,
132.3, 132.2, 130.9, 129.7, 129.6, 129.2, 128.6, 128.4, 124.8, 122.4,
122.3, 122.1, 120.3, 119.7, 112.7, 112.2, 100.3, 59.5, 20.9 (extra
peaks are present due to 13C–19F couplings).
9-Phenyl-14b,16-dihydroindolo[3′,4′:3,4,5]pyrido[2′,3′:6,7]aze-
pino[2,1-a]isoquinoline (3z)
Yield: 0.134 g (71%); yellow solid; mp 185–188 °C; Rf = 0.51
(EtOAc–hexane, 1:4).
IR (KBr): 3473, 3020, 2401, 1605 cm–1.
1H NMR (300 MHz, DMSO-d6): δ = 11.05 (s, 1 H), 8.45 (d, J = 3.7
Hz, 1 H), 8.12 (d, J = 7.4 Hz, 1 H), 7.66–7.61 (m, 2 H), 7.51 (d, J =
7.9 Hz, 1 H), 7.41–7.36 (m, 1 H), 7.28–7.25 (m, 1 H), 7.21–7.19 (m,
3 H), 7.06–7.03 (m, 3 H), 6.79 (d, J = 6.9 Hz, 2 H), 6.48 (s, 1 H),
6.16 (s, 1 H), 5.62 (s, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C29H21FN3: 430.1720; found:
13C NMR (100 MHz, DMSO-d6): δ = 154.6, 146.5, 142.9, 141.3,
137.3, 137.1, 136.7, 133.8, 133.7, 133.0, 129.8, 129.7, 129.5, 127.8,
127.0, 126.1, 125.5, 123.5, 122.1, 121.9, 121.6, 120.3, 112.2, 101.6,
59.8.
430.1714.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1553–1563