¨
F. R. WUST AND T. KNIESS
40
was evaporated to give the desired methanesulfonate esters 6 or 7, which were
used without further purification.
1
4-(1H-Indol-3-yl)butyl Methanesulfonate 6. Yield: 96%. H-NMR (CDCl3) d
1.84 (m, 4H, CH2), 2.82 (m, 2H, CH2), 2.95 (s, 3H, CH3), 4.24 (m, 2H, CH2),
6.99 (s, 1H), 7.12 (m, 1H, Ar-H), 7.20 (m, 1H, Ar-H), 7.36 (d, J = 8.1 Hz, 1H,
Ar-H), 7.59 (d, J=7.7 Hz, 1H, Ar-H), 8.05 (bs, 1H). LRMS (ESI positive) 268
[M+H].
4-[1-(4-Fluorophenyl)-1H-Indol-3-yl]butyl methanesulfonate 7. Yield: 92%.
1H-NMR (CDCl3) d 1.89 (m, 4H, CH2), 2.87 (m, 2H, CH2), 2.98 (s, 3H, CH3),
4.28 (m, 2H, CH2), 7.10 (s, 1H), 7.16–7.24 (m, 4H, Ar-H), 7.43–7.48 (m, 3H,
Ar-H), 7.66 (d, J=7.0 Hz, 1H, Ar-H). LRMS (ESI positive) 362 [M+H].
General procedure for the N-alkylation of methansulfonates 6 and 7 with amines
8 and 9 to give compounds 10, 11, 12 and 13. Amine 829 or 9 (10 mmol) and
Na2CO3 (4.7 mmol) were placed with water (2.5 ml) in a flask. Mesylate 6 or 7
in acetone (15 ml) was added to the amine/Na2CO3 slurry while stirring. The
mixture was stirred overnight at 508C. 10% NaHCO3-solution was added and
the mixture extracted with ethyl acetate. After removal of the solvent the
residue was purified by flash-chromatography (10% MeOH/CHCl3).
10-[4-(1H-Indol-3-yl)-1-butyl]spiro[isobenzofuran-1(3H),40-piperidine] 10. Yield:
1
59%. H-NMR (CDCl3) d 1.66 (m, 2H, CH2), 1.76 (m, 4H, CH2), 2.00 (td,
J=12.9, 4.2 Hz, 2H, CH2), 2.38 (t, J=10.9 Hz, 2H, CH2), 2.48 (m, 2H, CH2), 2.80
(t, J=7.3 Hz, 2H, CH2), 2.88 (m, 2H, CH2), 5.07 (s, 2H, CH2), 6.99 (s, 1H), 7.12
(m, 2H, Ar-H), 7.20 (m, 2H, Ar-H), 7.27 (m, 2H, Ar-H), 7.36 (d, J = 8.1Hz, 1H,
Ar-H), 7.59 (d, J = 7.7 Hz, 1H, Ar-H), 7.98 (bs, 1H). LRMS (ESI positive) 361
[M+H].
10-[4-[1-(4-Fluorophenyl)-1H-indol-3-yl]-1-butyl]spiro[isobenzofuran-1(3h),40-
1
piperidine] 11. Yield: 52%. H-NMR (CDCl3) d 1.71 (m, 2H, CH2), 1.79 (m,
4H, CH2), 2.05 (m, 2H, CH2), 2.42 (m, 2H, CH2), 2.51 (m, 2H, CH2), 2.85 (t,
J=7.0 Hz, 2H, CH2), 2.91 (m, 2H, CH2), 5.07 (s, 2H, CH2), 7.10 (s, 1H), 7.15
(m, 1H, Ar-H), 7.17 (m, 1H, Ar-H), 7.18–7.22 (m, 4H, Ar-H), 7.26–7.29 (m, 2H,
Ar-H), 7.43–7.47 (m, 3H, Ar-H), 7.66 (d, J=7.3 Hz, 1H). LRMS (ESI positive)
455 [M+H].
1
3-[4-(4-Phenyl-1-piperazinyl)-1-butyl]-1H-indole 12. Yield: 67%. H-NMR
(CDCl3) d 1.68 (m, 2H, CH2), 1.80 (m, 2H, CH2), 2.48 (m, 2H, CH2), 2.64 (m,
4H, CH2), 2.83 (t, J=7.3 Hz, 2H, CH2), 3.24 (m, 4H, CH2), 6. 89 (t, J=7.3 Hz,
1H, Ar-H), 6.96 (m, 2H, Ar-H), 6.97 (s, 1H), 7.15 (m, 1H, Ar-H), 7.21 (m, 1H,
Ar-H), 7.65 (d, J=7.7 Hz, 1H), 8.13 (bs, 1H). LRMS (ESI positive) 334
[M+H].
Copyright # 2004 John Wiley & Sons, Ltd.
J Label Compd Radiopharm 2005; 48: 31–43