1
13
H and C NMR spectra were recorded on Bruker Avance DRX and Varian UNITY-Plus spectrometers
using CDCl with TMS as internal standard. GC-MS (EI, 70 eV) was carried out on an HP GC/MS 5890/5892
3
instrument with an HP-5MS column. Hydrogenation was performed using one-liter Bergof BR-1000 autoclave.
3
-(1H-Pyrrol-1-yl)pyridine (2) [5]. A mixture of 2,5-dimethoxytetrahydrofuran (40 g, 0.3 mol),
3
-aminopyridine (3) (28 g, 0.3 mol) and acetic acid (150 ml) was refluxed for 12 h. The reaction mixture was
cooled to room temperature, poured into water (500 ml), and neutralized using 20% NaOH to pH ~ 7.5. The
product was extracted with dichloromethane (3200 ml) and the organic phase was dried over sodium sulfate.
Solvent was removed under reduced pressure and the residue was distilled in vacuo (20 mm Hg) at 135-137ºC.
1
Yield 40 g (92%). H NMR spectrum (500 MHz), , ppm (J, Hz): 6.41 (2H, t, J = 2.0, Н-3',4'); 7.10 (2H, t,
3
3
3
4
4
J = 2.0, Н-2',5'); 7.35 (1H, dd, J = 8.5, J = 4.5, Н-5); 7.70 (1H, ddd, J = 8.5, J = 2.5, J = 1.5, H-4); 8.51 (1H,
3
4
4
dd, J = 4.5, J = 1.5, H-6); 8.76 (1H, d, J = 2.5, H-2).
-(Pyrrolidin-1-yl)piperidine (1). 33% HCl (60 g, 0.53 mol) and 10% Pd/C (5 g) were added to a
3
solution of compound 2 (30 g, 0.21 mol) in MeOH (600 ml). The mixture was hydrogenated for 8 h at 70 atm.
and 100ºC. After cooling, the catalyst was separated by filtration, washed with MeOH (100 ml), and the solvent
was removed under reduced pressure. 2-PrOH (250 ml) and NaHCO (85 g, 1 mol) were added to the residue of
3
the dihydrochloride of compound 1 obtained and the suspension was refluxed for 1.5 h. The mixture was cooled
to 35ºC, filtered, washed with 2-PrOH (70 ml), and the filtrate was evaporated under reduced pressure. The
residue (the free base of the product 1) was distilled in vacuo (20 mm Hg) at 120-123ºC. Yield 30.0 g (93%).
1
H NMR spectrum (400 MHz), , ppm: 1.19–1.39 (2H, m); 1.53–1.68 (5H, m); 1.77 (1H, br. s); 1.85–1.96 (2H,
1
3
m); 2.34–2.48 (6H, m); 2.75–2.83 (1H, m); 3.04–3.12 (1H, m). C NMR spectrum (125 MHz), , ppm: 23.0
С-3',4'); 25.4 (С-5); 30.7 (С-4); 46.5 (С-6); 51.4 (С-2',5'); 51.8 (С-2); 62.33 (С-3). Mass spectrum, m/z (I , %):
(
1
rel
+
54 [M] (15), 110 (100), 97 (23), 84 (21), 69 (18), 55 (10), 41 (16). Found, %: С 70.19; Н 11.65; N 18.21.
C H N . Calculated, %: C 70.08; H 11.76; N 18.16.
9
18
2
REFERENCES
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1
2
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.
A. Mann in: C. G. Wermuth (editor), Practice of Medicinal Chemistry, 3 Ed., Elsevier, Amsterdam
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Z.-J. Liu, J.-P. Vors, E. R. F. Gesing, and C. Bolm, Green Chem., 13, 42 (2011).
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179