A. Büttner et al. / Bioorg. Med. Chem. 18 (2010) 3387–3402
3399
13C NMR (100 MHz, CD3OD): d = 21.0 (C1tetrahydrocarbazole), 27.2
(Ntetrahydrocarbazole–CH2–CH2–CH2), 27.3 (C4tetrahydrocarbazole), 28.4
CH2), 1.70–1.78 (m, 2H, Ntetrahydrocarbazole–CH2–CH2), 1.95–2.08
(m, 1H, C2tetrahydrocarbazoleH), 2.28–2.36 (m, 1H, C20tetrahydrocarbazoleH),
2.63 (t, 3J = 7.6 Hz, 2H, Ntetrahydrocarbazole–CH2–CH2–CH2–CH2–CH2),
2.69–2.75 (m, 1H, C4tetrahydrocarbazoleH), 2.87–2.94 (m, 2H,
C1tetrahydrocarbazoleH, C40tetrahydrocarbazoleH), 2.97 (t, 3J = 7.2 Hz, 2H, O–
CH2–CH2), 3.13–3.18 (m, 1H, C10tetrahydrocarbazoleH), 3.22 (s, 6H,
N(CH3)2), 3.57–3.64 (m, 1H, C3tetrahydrocarbazoleH), 3.98–4.09 (m, 2H,
Ntetrahydrocarbazole–CH2), 4.13 (t, 3J = 7.2 Hz, 2H, O–CH2–CH2), 6.73 (d,
3J = 8.4 Hz, 2H, C3phenolH, C3p0 henolH), 6.77 (dd, 3J = 8.4 Hz, 4J = 2.0 Hz,
1H, C7tetrahydrocarbazoleH), 6.89 (d, 4J = 2.4 Hz, 1H, C5tetrahydrocarbazoleH),
7.12 (d, 3J = 8.0 Hz, 2H, C3dimethylaminophenylH, C30dimethylaminophenylH),
7.17 (d, 3J = 8.8 Hz, 1H, C8tetrahydrocarbazoleH), 7.31 (d, 3J = 8.4 Hz, 2H,
C2phenolH, C20phenolH), 7.49 (d, 3J = 8.4 Hz, 2H, C2dimethylaminophenylH,
C20dimethylaminophenylH).
(Ntetrahydrocarbazole–CH2–CH2),
CH2–CH2–CH2), 32.4 (C2tetrahydrocarbazole), 35.7 (O–CH2–CH2), 36.1
(Ntetrahydrocarbazole–CH2–CH2–CH2–CH2–CH2), 43.9 (Ntetrahydrocarbazole
31.1
(Ntetrahydrocarbazole–CH2–
–
CH2), 49.1 (C3tetrahydrocarbazole), 55.7 (OCH3), 71.3 (O–CH2–CH2),
102.5 (C5tetrahydrocarbazole), 105.2 (C4atetrahydrocarbazole), 110.9
(C8tetrahydrocarbazole), 112.4 (C7tetrahydrocarbazole), 114.6 (C3methoxyphenyl
C30methoxyphenyl), 116.2 (C3phenol, C3p0 henol), 128.3 (C8atetrahydrocarbazole),
130.3 (C2methoxyphenyl
C20methoxyphenyl), 130.8 (C5acarbazol), 130.9
(C2phenol
C20phenol), 133.6 (C1phenol), 135.2 (C1atetrahydrocarbazole),
,
,
,
135.5 (C1methoxyphenyl), 154.2 (C6tetrahydrocarbazole), 156.8 (C4phenol),
159.1 (C4methoxyphenyl).
HRMS: [M+HꢁHCl]+ [C32H39N2O3]+, calcd: 499.29552, found:
499.29514.
13C NMR (75 MHz, CD3OD): d = 21.1 (C1tetrahydrocarbazole), 27.2
(Ntetrahydrocarbazole–CH2–CH2–CH2), 27.2 (C4tetrahydrocarbazole), 28.3
(Ntetrahydrocarbazole–CH2–CH2),
CH2–CH2–CH2), 31.9 (C2tetrahydrocarbazole), 35.8 (O–CH2–CH2), 36.1
(Ntetrahydrocarbazole–CH2–CH2–CH2–CH2–CH2), 43.8 (Ntetrahydrocarbazole
CH2), 47.2 (N(CH3)2), 49.2 (C3tetrahydrocarbazole), 71.2 (O–CH2–CH2),
102.4 (C5tetrahydrocarbazole), 105.3 (C4atetrahydrocarbazole), 110.9
31.0
(Ntetrahydrocarbazole–CH2–
4.5.4. 4-(2-(3-Amino-9-(5-(4-(trifluoromethyl)phenyl)pentyl)-
2,3,4,9-tetrahydro-1H-tetrahydrocarbazole-6-yloxy)ethyl)-
phenol hydrochloride 22
–
NH3Cl
(C8tetrahydrocarbazole), 112.4 (C7tetrahydrocarbazole), 116.2 (C3phenol
C30phenol), 121.3 (C3dimethylaminophenyl C3d0 imethylaminophenyl), 128.2
(C8atetrahydrocarbazole), 130.8 (C5atetrahydrocarbazole), 131.0 (C2phenol
C20phenol), 131.5 (C2dimethylaminophenyl C2d0 imethylaminophenyl), 133.6
,
,
O
,
,
N
HO
(C1phenol), 135.2 (C1atetrahydrocarbazole), 141.6 (C1dimethylaminophenyl),
146.4 (C4dimethylaminophenyl), 154.2 (C6tetrahydrocarbazole), 156.8
(C4phenol).
HRMS: [M+Hꢁ2HCl]+ [C33H42N3O2]+, calcd: 512.32715, found:
512.32730.
F3C
Reaction time:
Yield:
Mp:
10 h (coupling), 2 h (deprotection)
75 mg, (0.13 mmol, 60%)
125–128 °C
4.5.3. 4-(2-(3-Amino-9-(5-(4-methoxyphenyl)pentyl)-2,3,4,9-
tetrahydro-1H-tetrahydrocarbazole-6-yloxy)ethyl)phenol
hydrochloride 21
1H NMR (200 MHz, CD3OD): d = 1.21–1.38 (m, 2H, Ntetrahydrocarbazole
–
NH3Cl
CH2–CH2–CH2), 1.42–1.81 (m, 4H, Ntetrahydrocarbazole–CH2–CH2–CH2–
CH2), 1.90–2.17 (m, 1H, C2tetrahydrocarbazoleH), 2.20–2.38 (m, 1H,
C20tetrahydrocarbazoleH), 2.58 (t, 3J = 7.6 Hz, 2H, Ntetrahydrocarbazole
–
O
CH2–CH2–CH2–CH2–CH2), 2.67–2.76 (m, 1H, C4tetrahydrocarbazoleH),
2.79–2.88 (m, 2H, C1tetrahydrocarbazoleH, C40tetrahydrocarbazoleH), 2.93 (t,
3J = 7.0 Hz, 2H, O–CH2–CH2), 3.07–3.17 (m, 1H, C1t0etrahydrocarbazoleH),
3.42–3.63 (m, 1H, C3tetrahydrocarbazoleH), 3.97 (t, 3J = 6.8 Hz, 2H,
Ntetrahydrocarbazole–CH2), 4.10 (t, 3J = 7.0 Hz, 2H, O–CH2–CH2),
6.68–6.77 (m, 3H, C3phenolH, C3p0 henolH, C7tetrahydrocarbazoleH), 6.87
(d, 4J = 2.2 Hz, 1H, C5tetrahydrocarbazoleH), 7.08 (d, J = 8.6 Hz, 2H,
C2phenolH, C20phenolH), 7.14 (d, J = 8.8 Hz, 1H, C8tetrahydrocarbazoleH),
7.21 (d, J = 8.0 Hz, 2H, C2trifluoromethylphenylH, C20trifluoromethylphenylH),
7.46 (d, J = 8.2 Hz, 2H, C3trifluoromethylphenylH, C30trifluoromethylphenylH).
13C NMR (50 MHz, CD3OD): d = 21.0 (C1tetrahydrocarbazole), 27.2
(Ntetrahydrocarbazole–CH2–CH2–CH2), 27.4 (C4tetrahydrocarbazole), 28.4
(Ntetrahydrocarbazole–CH2–CH2), 31.0 (Ntetrahydrocarbazole–CH2–CH2–
CH2–CH2), 31.9 (C2tetrahydrocarbazole), 36.2 (O–CH2–CH2), 36.3
N
HO
O
Reaction time:
Yield:
18 h (coupling), 3 h (deprotection)
74 mg (0.14 mmol, 64%)
107–111 °C
Mp:
1H NMR (400 MHz, CD3OD): d = 1.27–1.33 (m, 2H, Ntetrahydrocarbazole
–
CH2–CH2–CH2), 1.46–1.59 (m, 2H, Ntetrahydrocarbazole–CH2–CH2–CH2–
CH2), 1.67–1.76 (m, 2H, Ntetrahydrocarbazole–CH2–CH2), 1.96–2.07 (m,
1H, C2tetrahydrocarbazoleH), 2.24–2.33 (m, 1H, C20tetrahydrocarbazoleH),
2.48 (t, J = 7.6 Hz, 2H, Ntetrahydrocarbazole–CH2–CH2–CH2–CH2–CH2),
2.68–2.74 (m, 1H, C4tetrahydrocarbazoleH), 2.82–2.89 (m, 2H,
C1tetrahydrocarbazoleH, C40tetrahydrocarbazoleH), 2.96 (t, 3J = 7.6 Hz, 2H,
O–CH2–CH2), 3.11–3.16 (m, 1H, C10tetrahydrocarbazoleH), 3.54–3.63 (m,
1H, C3tetrahydrocarbazoleH), 3.73 (s, 3H, OCH3), 3.93–4.04 (m, 2H,
Ntetrahydrocarbazole–CH2), 4.13 (t, 3J = 7.2 Hz, 2H, O–CH2–CH2), 6.71–
6.78 (m, 5H, C3methoxyphenylH, C30methoxyphenylH, C7carbazolH, C3phenolH,
C30phenolH), 6.88 (d, 4J = 2.4 Hz, 1H, C5tetrahydrocarbazoleH), 6.97 (d,
3J = 8.8 Hz, 2H, C2methoxyphenylH, C2m0 ethoxyphenylH), 7.11 (d, J = 8.4 Hz,
(Ntetrahydrocarbazole–CH2–CH2–CH2–CH2–CH2), 43.9 (Ntetrahydrocarbazole
CH2), 49.1 (C3tetrahydrocarbazole), 71.4 (O–CH2–CH2), 102.5
(C5tetrahydrocarbazole), 105.2 (C4atetrahydrocarbazole), 111.0
–
(C8tetrahydrocarbazole), 112.5 (C7tetrahydrocarbazole), 116.2 (C3phenol
,
C30phenol), 125.7–126.8 (m, C3trifluoromethylphenyl, C3t0rifluoromethylphenyl),
128.3 (C8atetrahydrocarbazole), 128.6–128.7 (m, CF3), 129.3
(C4trifluoromethylphenyl),
130.0
(C2trifluoromethylphenyl
,
C20trifluoromethylphenyl), 130.8 (C5atetrahydrocarbazole), 131.0 (C2phenol
,
C20phenol), 133.7 (C1phenol), 135.2 (C1atetrahydrocarbazole), 148.3
(C1trifluoromethylphenyl), 154.3 (C6tetrahydrocarbazole), 156.9 (C4phenol).
HRMS: [M+H–HCl]+ [C32H36N2O2F3]+, calcd: 537.27234, found:
537.27201.
2H,
C2phenolH,
C8cTetrahydrocarbazoleH).
C20phenolH),
7.17
(d,
3J = 8.8 Hz,
1H,