C. Jagusch et al. / Bioorg. Med. Chem. 16 (2008) 1992–2010
2003
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1
151.3 (dd, JCF = 15.4 Hz, JCF = 254.3 Hz, Cq), 155.3
(Cq); MS (ESI): m/z = 272 [M++H].
ethoxyphenylboronic acid (0.61 g, 3.36 mmol); yield:
0.47 g (94%); yellow solid: mp 114 ꢁC; Rf = 0.16
(EtOAc/MeOH 9:1); IR (ATR) t (cmꢀ1) 3110 (w),
3086 (w), 3002 (w), 2960 (w), 2926 (w), 2855 (w), 1596
(m), 1519 (m), 1477 (m), 1280 (m), 1150 (m), 1022 (s),
808 (s), 764 (s), 666 (m); dH (CDCl3, 500 MHz) 3.93 (s,
3H), 3.98 (s, 3H), 5.16 (s, 2H), 6.92 (br s, 1H), 6.94 (d,
J = 8.5 Hz, 1H), 7.11 (br s, 1H), 7.46 (dd, J = 2.2,
8.5 Hz, 1H), 7.47 (dd, J = 2.2, 8.5 Hz, 1H), 7.58 (br s,
1H), 7.65 (d, J = 2.2 Hz, 1H), 7.67 (d, J = 8.5 Hz, 1H),
8.54 (d, J = 2.2 Hz, 1H); dC (CDCl3, 125 MHz) 48.1
(CH2), 56.0 (CH3), 56.0 (CH3), 113.3 (CH), 110.0
(CH), 111.1 (CH), 119.0 (CH), 119.5 (CH), 120.0
(CH), 129.4 (Cq), 130.3 (CH), 131.4 (Cq) 135.7 (CH),
148.4 (CH), 149.4 (Cq), 150.3 (Cq), 157.3 (Cq); MS
(ESI): m/z = 296 [M++H].
5.4.3.5. 5-((1H-Imidazol-1-yl)methyl)-2-(4-methoxy-
phenyl)pyridine (5). Synthesised according to Method
B using compound 1a (0.40 g, 1.68 mmol) and 4-meth-
oxyphenylboronic acid (0.38 g, 3.35 mmol); yield:
0.40 g (89%); yellow solid: mp 138 ꢁC; Rf = 0.15
(EtOAc/MeOH, 9:1); IR (ATR) t (cmꢀ1) 2962 (w),
2928 (w), 1597 (m), 1478 (m), 1249 (s), 1174 (m), 1023
(m), 828 (s), 814 (s), 762 (s); dH (CDCl3, 500 MHz)
3.86 (s, 3H), 5.16 (s, 2H), 6.92 (t, J = 1.3 Hz, 1H), 6.99
(d, J = 9.1 Hz, 2H), 7.11 (s, 1H), 7.46 (dd, J = 2.5,
8.2 Hz, 1H), 7.59 (s, 1H), 7.66 (d,J = 8.2 Hz, 1H), 7.94
(d, J = 9.1 Hz, 2H), 8.54 (d, J = 2.5 Hz, 1H); dC (CDCl3,
125 MHz) 48.1 (CH2), 55.4 (CH3), 114.2 (CH), 119.0
(CH), 119.8 (CH), 128.2 (CH), 129.2 (Cq), 130.3 (CH),
131.2 (Cq), 135.7 (CH), 137.3 (CH), 148.5 (CH), 157.4
(Cq), 160.8 (Cq); MS (ESI): m/z = 266 [M++H].
5.4.3.9. 2-((1H-Imidazol-1-yl)methyl)-5-(4-fluorophe-
nyl)pyridine (9). Synthesised according to Method B
using compound 9a (0.20 g, 0.84 mmol) and 4-fluor-
ophenylboronic acid (0.23 g, 1.68 mmol); yield: 0.18 g
(83%); yellow solid: mp 90 ꢁC; Rf = 0.11 (EtOAc/
MeOH, 9:1); IR (ATR) t (cmꢀ1) 3116 (w), 3046 (w),
2927 (w), 1064 (m), 1519 (m), 1486 (s), 1393 (w), 1220
(s), 1163 (m), 1070 (s), 906 (w), 828 (s), 817 (s), 769
(s), 684 (s), 660 (s); dH (CDCl3, 500 MHz) 5.29 (s, 2H),
7.02 (m, 2H), 7.14 (br s, 1H), 7.17 (t, J = 8.8 Hz, 2H),
7.52 (dd, J = 5.4, 8.8 Hz, 1H), 7.65 (s, 1H), 7.79 (dd,
J = 2.2, 8.2 Hz, 2H), 8.76 (d, J = 2.2 Hz, 1H); dC
(CDCl3, 125 MHz) 52.3 (CH2), 116.2 (d, 2JCF = 22.1 Hz,
5.4.3.6. 5-((1H-Imidazol-1-yl)methyl)-2-(2-methoxy-
phenyl)pyridine (6). Synthesised according to Method
B using compound 1a (0.20 g, 0.84 mmol) and 2-meth-
oxyphenylboronic acid (0.19 g, 1.68 mmol); yield:
0.21 g (92%); yellow solid: mp 103 ꢁC; Rf = 0.15
(EtOAc/MeOH, 9:1); IR (ATR) t (cmꢀ1) 2924 (m),
2854 (m), 1598 (m), 1477 (s), 1395 (m), 1261 (m), 1237
(s), 1079 (m), 1022 (s), 835 (m), 795 (s), 665 (s); dH
(CDCl3, 500 MHz) 3.85 (s, 3H), 5.17 (s, 2H), 6.95 (br
s, 1H), 7.00 (dd, J = 0.6, 8.5 Hz, 1H), 7.08 (dt, J = 1.1,
7.6 Hz, 1H), 7.12 (s, 1H), 7.38 (ddd, J = 1.9, 7.6,
8.5 Hz, 1H), 7.44 (dd, J = 2.2, 8.5 Hz, 1H), 7.60 (s,
1H), 7.77 (dd, J = 1.9, 7.6 Hz, 1H), 7.83 (d, J = 8.2 Hz,
1H), 8.60 (d, J = 1.6 Hz, 1H); dC (CDCl3, 125 MHz)
48.2 (CH2), 55.6 (CH3), 111.4 (CH), 119.1 (CH), 121.1
(CH), 125.2 (CH), 128.3 (Cq), 129.5 (Cq), 130.2 (CH),
130.3 (CH), 131.1 (CH), 134.6 (CH), 137.3 (CH), 148.2
(CH), 156.4 (Cq), 157.0 (Cq); MS (ESI): m/z = 266
[M++H].
3
CH), 119.5 (CH), 121.1 (CH), 128.8 (d, JCF = 8.6 Hz,
CH), 130.0 (CH), 130.4 (CH), 133.2 (d, JCF = 3.8 Hz,
4
Cq), 135.2 (Cq), 135.4 (CH), 148.0 (CH), 154.9 (Cq),
163.0 (d, JCF = 247.6 Hz, Cq); MS (ESI): m/z = 254
1
[M++H].
5.4.3.10. 4-Phenylthiophene-2-carbaldehyde (10b).
Synthesised according to Method B using phenylboronic
acid (0.49 g, 2.00 mmol) and 4-bromothiophen-2-carbal-
dehyde (0.38 g, 2.00 mmol); yield: 0.35 g (93%); white
solid: mp 57–58 ꢁC; Rf = 0.39 (PE/EtOAc, 10:1); IR
(ATR) t (cmꢀ1) 3096 (w), 2838 (w), 1670 (s), 1597 (w),
1430 (m), 1247 (w), 1180 (s), 1048 (w), 755 (s), 695
(m), 660 (s); dH (CDCl3, 500 MHz) 7.36 (m, 1H), 7.44
(dd, J = 7.3, 7.9 Hz, 2H), 7.59 (dd, J = 1.3 Hz, 8.5 Hz,
2H), 7.85 (dd, J = 1.3 Hz, 1.6 Hz, 1H), 8.03 (d,
J = 1.6 Hz, 1H), 9.97 (d, J = 1.3 Hz, 1H); dC (CDCl3,
125 MHz) 115.3 (CH), 126.3 (CH), 128.0 (CH), 129.1
(CH), 129.6 (CH), 134.4 (Cq), 143.7 (Cq), 144.4 (Cq),
183.0 (CH); MS (ESI): m/z = 189 [M++H].
5.4.3.7. 3-(5-((1H-Imidazol-1-yl)methyl)pyridin-2-yl)ben-
zeneamine (7). Synthesised according to Method B using
compound 1a (0.20 g, 0.84 mmol) and 2-meth-
oxyphenylboronic acid (0.29 g, 1.68 mmol); yield:
0.14 g (67%); orange solid: mp 145 ꢁC; Rf = 0.11
(EtOAc/MeOH, 9:1); IR (ATR) t (cmꢀ1) 3406 (w),
3408 (w), 3323 (w), 3212 (w), 2957 (m), 2924 (m), 2854
(m), 1630 (m), 1600 (s), 1476 (s), 1235 (m), 1105 (s),
1073 (s), 1026 (s), 787 (s), 758 (s); dH (CDCl3,
500 MHz) 5.11 (s, 2H), 6.72 (ddd, J = 0.9, 2.4, 7.6 Hz,
1H), 6.89 (br s, 1H), 7.08 (br s, 1H), 7.21 (t, J = 7.7
Hz, 1H), 7.28 (dt, J = 1.3, 7.8 Hz, 1H), 7.33 (t,
J = 2.2 Hz, 1H), 7.41 (dd, J = 2.2, 8.2 Hz, 1H), 7.55
(br s, 1H), 7.62 (d, J = 8.2 Hz, 1H), 8.50 (d,
J = 2.2 Hz, 1H); dC (CDCl3, 125 MHz) 48.0 (CH2),
113.3 (CH), 116.0 (CH), 117.0 (CH), 119.0 (CH), 120.5
(CH), 129.6 (CH), 129.9 (Cq), 130.1 (CH), 135.6 (CH),
137.2 (CH), 139.5 (Cq), 146.9 (Cq), 148.3 (CH) 157.6
(Cq); MS (ESI): m/z = 251 [M++H].
5.4.3.11. 4-(4-Fluorophenyl)-thiophene-2-carbaldehyde
(11b). Synthesised according to Method B using 4-fluor-
ophenylboronic acid (0.56 g, 4.00 mmol) and 4-bromo-
thiophen-2-carbaldehyde (0.38 g, 2.00 mmol); yield:
0.38 g (92%); white solid: mp 76–78 ꢁC; Rf = 0.34 (PE/
EtOAc, 10:1); IR (ATR) t (cmꢀ1) 2945 (w), 2839 (w),
1665 (s), 1547 (m), 1507 (s), 1435 (m), 1228 (s), 1216
(s), 1181 (m), 829 (s), 666 (s), 566 (s); dH (CDCl3,
500 MHz) 7.13 (dd, J = 8.5, 8.8 Hz, 2H), 7.55 (dd,
J = 5.4, 8.8 Hz, 2H), 7.79 (dd, J = 1.3, 1.6 Hz, 1H),
7.98 (d, J = 1.6 Hz, 1H), 9.97 (d, J = 1.3 Hz, 1H); dC
5.4.3.8. 5-((1H-Imidazol-1-yl)methyl)-2-(3,4-dimethoxy-
phenyl)pyridine (8). Synthesised according to Method B
using compound 1a (0.40 g, 1.68 mmol) and 3,4-dim-
2
(CDCl3, 125 MHz) 116.0 (d, JCF = 22.1 Hz, CH),