mmol gϪ1) in dichloromethane (4 mL) gave the title compound
(50 mg, 42%); νmax/cmϪ1 2925, 1692, 1602, 1420, 1116, 808 and
716; δH (400 MHz; CDCl3) 1.70–2.10 (3H, m, C(3)-Ha and
C(4)-H2), 2.15–2.30 (2H, m, C(3)-Hb and C(5)-Ha), 3.18 (1H,
d, J 14.1, NCHa-4-Py), 3.40–3.55 (2H, m, C(2)-H and C(5)-
Hb), 3.77 (1H, d, J 14.1, NCHb-4-Py), 7.23 (2H, d, J 5.2, C(2Љ)-
H and C(6Љ)-H), 7.27 (1H, br d, J 7.9, C(5Ј)-H), 7.80 (1H, d,
J 7.9, C(4Ј)-H), 8.45–8.55 (1H, m, C(6Ј)-H), 8.50 (2H, d, J 5.2,
C(3Љ)-H and C(5Љ)-H), 8.63 (1H, s, C(2Ј)-H); δC (100 MHz;
CDCl3) 22.65 (C(4)H2), 35.08 (C(3)H2), 53.66 (C(5)H2), 57.08
(NCH2-4-Py), 67.20 (C(2)H), 123.52 (C(2Љ)H and C(6Љ)H),
123.73 (C(5Ј)H), 135.09 (C(4Ј)H), 138.77 (C(3Ј)), 146.82
(C(1Љ)), 148.71 (C(6Ј)H), 149.36 (C(2Ј)H), 150.08 (C(3Љ)H and
C(5Љ)H); MS(EI) m/z 239.14 (Mϩ).
128.18 (C(3Љ)H and C(5Љ)H), 128.54 (C(2Љ)H and C(6Љ)H),
137.88 and 138.98 (C(3Ј) and C(1Љ)), 139.63 (C(4Ј)H), 149.24
(C(2Ј)H), 151.27 (C(6Ј)); MS(EI) m/z 272.11 (Mϩ).
Preparation of 3-(1-methylpyrrol-2-yl)pyridine 17a; general
procedure for 3-(1-substituted pyrrol-2-yl)pyridine
To a stirred solution of 4-(3-pyridyl)-4-oxobutyraldehyde
(0.10 g, 0.61 mmol) in dichloromethane (2 mL) was added
methylamine (0.61 mL, 1.2 mmol of 2.0 M solution in meth-
anol) at ambient temperature. The reaction mixture was stirred
at ambient temperature for 1 h and concentrated under reduced
pressure to yield the title compound (95 mg, 98%) as a pale
yellow oil; νmax/cmϪ1 2933, 1649, 1450, 1121, 1023 and 710; δH
(400 MHz; CDCl3) 3.60 (3H, s, NCH3), 6.15 (1H, dd, J 3.5, 3.0,
C(4)-H), 6.22 (1H, dd, J 3.5, 1.7, C(3)-H), 6.70 (1H, br s, C(5)-
H), 7.25 (1H, dd, J 7.9, 4.9, C(5Ј)-H), 7.63 (1H, br d, J 7.9,
C(4Ј)-H), 8.44 (1H, dd, J 4.9, 1.7, C(6Ј)-H), 8.60 (1H, d, J 1.7,
C(2Ј)-H); δC (100 MHz; CDCl3) 35.47 (NCH3), 108.64 (C(4)H),
110.21 (C(3)H), 123.63 (C(5Ј)H), 125.16 (C(5)H), 129.73 (C(2)),
131.20 (C(3Ј)), 135.90 (C(4Ј)H), 148.06 (C(6Ј)H), 149.62
(C(2Ј)H); MS(EI) m/z 158.08 (Mϩ).
Preparation of 3-(1-furfurylpyrrolidin-2-yl)pyridine 11m
Following the general procedure described above, furfuryl-
amine (97 mg, 1.0 mmol), 4-(3-pyridyl)-4-oxobutyraldehyde
(80 mg, 0.5 mmol), acetic acid (0.2 mL) and polymer-supported
cyanoborohydride (0.30 g, 1.0 mmol, 3.0 mmol gϪ1) in dichloro-
methane (4 mL) gave the title compound (60 mg, 53%); νmax
/
cmϪ1 2966, 2806, 1675, 1577, 1426, 1148, 1013, 806, 733 and
720; δH (400 MHz; CDCl3) 1.55–1.65 (1H, m, C(3)-Ha), 1.65–
1.75 (1H, m, C(4)-Ha), 1.75–1.92 (1H, m, C(4)-Hb), 2.05–2.15
(1H, m, C(3)-Hb), 2.37 (1H, dd, J 17.7, 8.9, C(5)-Ha), 3.12 (1H,
td, J 17.7, 2.3, C(5)-Hb), 3.24 (1H, d, J 14.3, NCHa-2-Furan),
3.32 (1H, t, J 8.1, C(2)-H), 3.60 (1H, d, J 14.3, NCHb-2-Furan),
5.98 (1H, d, J 3.0, C(3Љ)-H), 6.16 (1H, dd, J 3.0, 1.9, C(4Љ)-H),
7.16 (1H, dd, J 7.9, 4.6, C(5Ј)-H), 7.22 (1H, d, J 1.9, C(5Љ)-H),
7.67 (1H, br d, J 7.9, C(4Ј)-H), 8.39 (1H, br d, J 4.6, C(6Ј)-H),
8.48 (1H, br s, C(2Ј)-H); δC (100 MHz; CDCl3) 22.87 (C(4)H2),
35.60 (C(3)H2), 49.58 (NCH2-2-Furan), 53.87 (C(5)H2), 66.18
(C(2)H), 108.47 (C(3Љ)H), 110.39 (C(4Љ)H), 123.98 (C(5Ј)H),
135.26 (C(4Ј)H), 139.29 (C(3Ј)), 142.21 (C(5Љ)H), 148.97
(C(6Ј)H), 150.00 (C(2Ј)H), 152.87 (C(2Љ)); MS(EI) m/z 228.13
(Mϩ).
Preparation of 3-(1-ethylpyrrol-2-yl)pyridine 17b
By the general procedure described above, ethylamine (55 mg,
1.23 mmol) and 4-(3-pyridyl)-4-oxobutyraldehyde (100 mg,
0.613 mmol) in dichloromethane (2 mL) gave the title com-
pound (100 mg, 95%); νmax/cmϪ1 2974, 2932, 2677, 1652, 1585,
1473, 1397, 1025, 800 and 715; δH (400 MHz; CDCl3) 1.26 (3H,
t, J 7.3, NCH2CH3), 3.90 (2H, q, J 7.3, NCH2CH3), 6.17 (2H, br
s, C(3)-H and C(4)-H), 6.77 (1H, t, J 2.1, C(5)-H), 7.25 (1H, dd,
J 7.8, 4.9, C(5Ј)-H), 7.61 (1H, dt, J 7.8, 1.8, C(4Ј)-H), 8.47 (1H,
dd, J 4.9, 1.8, C(6Ј)-H), 8.58 (1H, d, J 1.8, C(2Ј)-H); δC (100
MHz; CDCl3) 17.10 (NCH2CH3), 42.33 (NCH2CH3), 108.81
(C(4)H), 110.25 (C(3)H), 122.74 (C(5)H), 123.64 (C(5Ј)H),
129.98 (C(2)), 130.57 (C(3Ј)), 136.16 (C(4Ј)H), 148.17 (C(6Ј)H),
149.77 (C(2Ј)H); MS(EI) m/z 173.10 (Mϩ).
Preparation of 3-(1-methylpyrrolidin-2-yl)-6-chloropyridine 11n
Preparation of 3-(1-benzylpyrrol-2-yl)pyridine 17c
Following the general procedure described above, methylamine
(0.195 mL, 0.39 mmol of 2.0 M solution in THF), 4-(6-chloro-
pyridin-3-yl)-4-oxobutyraldehyde (70 mg, 0.35 mmol), acetic
acid (0.1 mL) and sodium triacetoxyborohydride (112 mg,
0.53 mmol) in dichloromethane (2 mL) gave the title compound
(46 mg, 49%); νmax/cmϪ1 2916, 1709, 1563, 1395, 1256, 1106,
1012, 836 and 750; δH (400 MHz; CDCl3) 1.80–2.20 (4H, m,
C(3)-H2 and C(4)-H2), 2.40 (1H, q, J 9.1, C(5)-Ha), 2.53 (3H, s,
NCH3), 3.20–3.30 (1H, m, C(2)-H), 3.35–3.45 (1H, m, C(5)-
Hb), 7.27 (1H, d, J 8.3, C(5Ј)-H), 7.74 (1H, dd, J 8.3, 2.4, C(4Ј)-
H), 8.26 (1H, d, J 2.4, C(2Ј)-H); δC (100 MHz; CDCl3) 22.11
(C(4)H2), 33.95 (C(3)H2), 39.57 (NCH3), 56.30 (C(5)H2), 68.31
(C(2)H), 124.56 (C(5Ј)H), 135.12 (C(3Ј)), 138.31 (C(4Ј)H),
149.46 (C(2Ј)H), 150.86 (C(6Ј)H); MS(EI) m/z 196.08 (Mϩ).
Following the general procedure described above, benzylamine
(54 mg, 0.5 mmol) and 4-(3-pyridyl)-4-oxobutyraldehyde
(80 mg, 0.50 mmol) in dichloromethane (2 mL) gave the title
compound (117 mg, quantitative); νmax/cmϪ1 2929, 1689, 1656,
1453, 1312, 1024 and 715; δH (400 MHz; CDCl3) 5.05 (2H, s,
NCH2Ph), 6.23 (1H, dd, J 6.0, 3.2, C(3)-H), 6.25 (1H, br s,
C(4)-H), 6.74 (1H, br s, C(5)-H), 6.89 (2H, d, J 7.1, C(2Љ)-H and
C(6Љ)-H), 7.10–7.23 (4H, m, C(5Ј)-H, C(3Љ)-H, C(4Љ)-H and
C(5Љ)-H), 7.48 (1H, d, J 7.8, C(4Ј)-H), 8.40 (1H, d, J 4.4, C(6Ј)-
H), 8.52 (1H, s, C(2Ј)-H); δC (100 MHz; CDCl3) 51.28
(NCH2Ph), 109.29 (C(4)H), 110.63 (C(3)H), 123.54 (C(5Ј)H),
124.55 (C(5)H), 126.67 (C(2Љ)H and C(6Љ)H), 127.94 (C(4Љ)H),
129.19 (C(3Љ)H and C(5Љ)H), 129.66 (C(2)), 131.47 (C(3Ј)),
136.10 (C(4Ј)H), 138.67 (C(1Љ)), 148.40 (C(6Ј)H), 149.95
(C(2Ј)H); MS(EI) m/z 235.12 (Mϩ).
Preparation of 3-(1-benzylpyrrolidin-2-yl)-6-chloropyridine 11o
Preparation of 3-[1-(4-methoxybenzyl)pyrrol-2-yl]pyridine 17d
Following the general procedure described above, benzylamine
(22 mg, 0.2 mmol), 4-(6-chloropyridin-3-yl)-4-oxobutyralde-
hyde (40 mg, 0.2 mmol), acetic acid (0.1 mL) and polymer-
supported cyanoborohydride (0.13 g, 0.4 mmol, 3.0 mmol gϪ1)
in dichloromethane (2 mL) gave the title compound (25 mg,
46%); νmax/cmϪ1 2924, 1727, 1586, 1454, 1131 and 1120; δH
(400 MHz; CDCl3) 1.60–1.75 (1H, m, C(3)-Ha), 1.75–1.95 (2H,
m, C(4)-H2), 2.15–2.33 (2H, m, C(3)-Hb and C(5)-Ha), 3.05–
3.15 (1H, m, C(5)-Hb), 3.14 (1H, d, J 13.1, NCHaPh), 3.43 (1H,
dd, J 8.2, 8.1, C(2)-H), 3.75 (1H, d, J 13.1, NCHbPh), 7.20–7.32
(6H, m, C(5Ј)-H and NCH2C6H5), 7.78 (1H, dd, J 8.1, 2.0,
C(4Ј)-H), 8.40 (1H, d, J 2.0, C(2Ј)-H); δC (100 MHz; CDCl3)
22.57 (C(4)H2), 35.30 (C(3)H2), 53.38 (C(5)H2), 58.11
(NCH2Ph), 66.08 (C(2)H), 124.23 (C(5Ј)H), 126.91 (C(4Љ)H),
Following the general procedure described above, 4-methoxy-
benzylamine (42 mg, 0.31 mmol) and 4-(3-pyridyl)-4-oxo-
butyraldehyde (50 mg, 0.31 mmol) in dichloromethane (2 mL)
gave the title compound (82 mg, quantitative); νmax/cmϪ1 2931,
2835, 1638, 1611, 1513, 1250, 1176, 1033, 815 and 716; δH
(400 MHz; CDCl3) 3.56 (3H, s, C6H4OCH3), 4.86 (2H, s,
NCH2Ph), 6.08 (1H, dd, J 3.5, 2.9, C(4)-H), 6.11 (1H, dd, J 3.5,
1.8, C(3)-H), 6.60 (1H, d, J 2.9, C(5)-H), 6.60 (2H, d, J 8.7,
C(3Љ)-H and C(5Љ)-H), 6.70 (2H, d, J 8.7, C(2Љ)-H and C(6Љ)-H),
7.03 (1H, dd, J 7.9, 4.8, C(5Ј)-H), 7.37 (1H, br d, J 7.9, C(4Ј)-
H), 8.28 (1H, dd, J 4.8, 1.2, C(6Ј)-H), 8.39 (1H, d, J 1.2, C(2Ј)-
H); δC (100 MHz; CDCl3) 50.82 (NCH2Ph), 55.66
(C6H4OCH3), 109.14 (C(4)H), 110.60 (C(3)H), 114.58 (C(3Љ)H
152
J. Chem. Soc., Perkin Trans. 1, 2002, 143–154