J. Fournier dit Chabert et al. / Bioorg. Med. Chem. 15 (2007) 4482–4497
4491
7.86 (ddd, 1H, J = 1.5; 1.5; 7.9 Hz), 8.63 (dd, 1H, J = 1.5;
4.9 Hz), 7.94 (d, 1H, J = 1.5 Hz); dC (75 MHz, CDCl3)
71.4 (q, CH2, J = 36 Hz), 116.9 (C), 121.9 (CH), 122.6 (q,
CF3, J = 279 Hz), 122.7 (CH), 123.6 (CH), 125.5 (CH),
124.6 (CH), 125.5 (CH), 128.7 (C), 131.9 (C), 136.9 (C),
137.1 (CH), 148.7 (CH), 150.4 (CH), 157.9 (C) ppm; m/z
309 (M+, 70), 226 (50), 198 (100).
C10H9NOS: C 62.80, H 4.74, N 7.32%; dH (300 MHz,
CDCl3) 3.99 (s, 3H, OCH3), 6.93 (d, 1H, J = 5.6 Hz),
7.05 (ddd, 1H, J = 1.1; 4.9; 7.5 Hz), 7.28 (d, 1H,
J = 5.6 Hz), 7.65 (ddd, 1H, J = 1.9; 7.5; 8.0 Hz), 8.08
(ddd, 1H, J = 0.9; 1.1; 8.0 Hz), 8.53 (ddd, 1H, J = 0.9;
1.9; 4.9 Hz); dC (75 MHz, CDCl3) 58.9 (OCH3), 117.2
(CH), 120.7 (CH), 121.0 (CH), 121.6 (C), 126.1 (CH),
136.7 (CH), 149.4 (CH), 152.7 (C), 155.9 (C) ppm; m/z
191 (M+1, 50), 190 (M+, 50), 162 (100).
5.1.2.11. 2-(2,2,2-Trifluoroethoxy)-3-(20-cyanophenyl)-
benzo[b]thiophene (22). This was prepared in 69% yield
according to method C. Pale pink solid; mp 130–
131 ꢂC; dH (300 MHz, CDCl3) 4.48 (dq, 1H, J = 7.9;
11.9 Hz), 4.69 (dq, 1H, J = 8.1; 11.9 Hz), 7.33–7.43 (m,
3H), 7.48–7.59 (m, 2H), 7.68–7.78 (m, 2H), 7.83 (d,
1H, J = 7.7 Hz); dC (75 MHz, CDCl3) 71.0 (q, CH2,
J = 36 Hz), 113.9 (C), 116.4 (C), 118.5 (C), 121.8
(CH), 122.7 (CH), 124.6 (CH), 125.5 (CH), 125.9 (q,
CF3, J = 264 Hz), 128.4 (CH), 131.3 (CH), 131.7 (C),
132.9 (CH), 133.6 (CH), 136.5 (C), 136.9 (C), 158.6
(C) ppm; m/z 333 (M+, 40), 250 (30), 222 (100).
5.1.2.16. 2-(30-Pyridyl)-3-cyanothiophene (28). This
was prepared in 33% yield according to method B. Yel-
low powder; mp 119–120 ꢂC; Anal. found: C 64.19, H
3.23, N 14.43%, calcd for C10H6N2S: C 64.49, H 3.25,
N
15.04%; dH (300 MHz, CDCl3) 7.34 (d, 1H,
J = 5.3 Hz), 7.42 (d, 1H, J = 5.3 Hz), 7.43 (ddd, 1H,
J = 0.8; 4.9; 8.0 Hz), 8.12 (ddd, 1H, J = 1.8; 2.2;
8.0 Hz), 8.67 (dd, 1H, J = 1.8; 4.9 Hz), 8.93 (d, 1H,
J = 2.2 Hz); dC (75 MHz, CDCl3) 107.7 (C), 115.3 (C),
123.9 (CH), 126.8 (CH), 127.7 (C), 130.7 (CH), 134.9
(CH), 148.5 (CH), 149.6 (C), 150.7 (CH) ppm; m/z 186
(M+, 100), 159 (20).
5.1.2.12. 2-(20-Cyanophenyl)-3-methoxythiophene (23).
This was prepared in 51% yield according to method B.
Yellow oil; Anal. found: C 67.13, H 4.46, N 6.45%, calcd
for C12H9NOS: C 66.95, H 4.21, N 6.51%; dH (300 MHz,
CDCl3) 3.93 (s, 3H, OCH3), 6.97 (d, 1H, J = 5.5 Hz), 7.34
(d, 1H, J = 5.5 Hz), 7.37 (ddd, 1H, J = 1.3; 6.8; 7.7 Hz),
7.55 (ddd, 1H, J = 0.7; 1.3; 7.5 Hz), 7.59 (ddd, 1H,
J = 1.3; 6.8; 7.5 Hz), 7.72 (ddd, 1H, J = 0.7; 1.3; 7.5 Hz);
dC (75 MHz, CDCl3) 58.6 (OCH3), 112.9 (C), 116.5
(CH), 118.8 (C), 125.3 (CH), 127.4 (CH), 131.4 (CH),
132.6 (CH), 133.8 (CH), 136.5 (CH), 142.8 (C), 155.0
(C) ppm; m/z 215 (M+, 100), 200 (65), 186 (20).
5.1.2.17. 2-(Phenyl)-5-(400-chlorophenyl)-thiophene-3-
carboxaldehyde (29). This was prepared in 43% yield
according to method B. Beige oil; dH (300 MHz, CDCl3)
7.37 (d, 2H, J = 8.5 Hz), 7.47–7.53 (m, 6H), 7.56 (d, 2H,
J = 8.5 Hz), 9.86 (s, 1H, CHO); dC (75 MHz, CDCl3)
122.2 (CH), 126.0 (C), 127.2 (2CH), 129.1 (C), 129.2
(2CH), 129.4 (2CH), 129.8 (CH), 130.1 (2CH), 131.3
(C), 131.7 (C), 138.1 (C), 155.7 (C), 185.9 (CHO) ppm;
m/z 300 (40, M+2), 299 (40, M+1), 298 (100, M+), 297
(70), 270 (40), 234 (30); SMHR CI found: 299.0296,
calcd for C17H11ClOS,H+: 299.0297.
5.1.2.13. 2-(30-Pyridyl)-3-methoxythiophene (24). This
was prepared in 68% yield according to method C. Col-
ourless oil; Anal. found: C 63.03, H 4.97, N 7.45%, calcd
for C10H9NOS: C 62.80, H 4.74, N 7.32%; dH (300 MHz,
CDCl3) 3.94 (s, 3H, OCH3), 6.95 (d, 1H, J = 5.6 Hz), 7.23
(d, 1H, J = 5.6 Hz), 7.28 (dd, 1H, J = 4.0; 8.0 Hz), 8.00
(ddd, 1H, J = 0.6; 2.3; 8.0 Hz), 8.43 (d, 1H, J = 4.0 Hz),
8.97 (s, 1H); dC (75 MHz, CDCl3) 58.4 (OCH3), 115.6
(C), 117.0 (CH), 123.1 (CH), 123.3 (CH), 129.6 (C),
133.3 (CH), 146.7 (CH), 147.2 (CH), 154.8 (C) ppm; m/z
191 (M+, 100), 176 (40), 148 (40).
5.1.2.18.
2-(Phenyl)-5-(300-pyridyl)-thiophene-3-car-
boxaldehyde (30). This was prepared in 37% yield from
compound 27 according to method C. Yellow powder;
mp 129–130 ꢂC; dH (300 MHz, CDCl3) 7.35–7.65 (m,
6H), 7.81 (s, 1H), 7.91 (ddd, 1H, J = 1.7; 1.9; 7.9 Hz),
8.57 (d, 1H, J = 3.6 Hz), 8.89 (br s, 1H), 9.87 (s, 1H,
CHO); dC (75 MHz, CDCl3) 123.2 (CH), 123.9 (CH),
129.2 (2CH), 129.9 (CH), 130.2 (2CH), 131.1 (C),
133.2 (CH), 137.4 (C), 138.1 (C), 139.8 (C), 147.0
(CH), 149.4 (CH), 156.1 (C), 185.7 (CHO) ppm; m/z
265 (M+,100), 264 (80), 237 (20); SMHR CI found:
266.0641, calcd for C16H11NOS,H+: 266.0640.
5.1.2.14. 2,5-Di(30-pyridyl)-3-methoxythiophene (25).
Isolated as a by-product of the previous synthesis (53 mg)
as yellow viscous solid (yield = 16%); dH (300 MHz,
CDCl3) 3.97 (s, 3H, OCH3), 7.20 (s, 1H), 7.27 (dd, 1H,
J = 4.9; 8.1 Hz), 7.29 (dd, 1H, J = 4.9; 7.9 Hz), 7.83
(ddd, 1H, J = 1.4; 2.1; 8.1 Hz), 8.03 (ddd, 1H, J = 1.3;
1.9; 7.9 Hz), 8.44 (dd, 1H, J = 1.4; 4.9 Hz), 8.53 (dd, 1H,
J = 1.3; 4.9 Hz), 8.85 (d, 1H, J = 2.1 Hz), 8.94 (d, 1H,
J = 1.9 Hz); dC (75 MHz, CDCl3) 58.6 (OCH3), 113.8
(CH), 116.6 (C), 123.5 (CH), 123.6 (CH), 129.1 (C),
129.5 (C), 133.1 (CH), 134.1 (CH), 136.9 (C), 146.0
(CH), 147.2 (CH), 147.9 (CH), 149.1 (CH), 155.1 (C)
ppm; m/z 268 (M+, 100), 253 (80), 225 (30), 122 (80).
5.1.2.19. 2-(30-pyridyl)-5-(300-(a,a, a)-trifluorotoluyl)-3-
cyanothiophene (31). This was prepared in 42% yield from
compound 28according to method C. Yellowpowder; mp
145–146 ꢂC; Anal. found: C 61.62, H 3.07, N 8.29%, calcd
for C17H9F3N2S: C 61.81, H 2.75, N 8.48%; dH (300 MHz,
CDCl3) 7.46 (ddd, 1H, J = 0.6; 4.9; 7.9 Hz), 7.56 (s, 1H),
7.60 (m, 1H), 7.65 (d, 1H, J = 7.9 Hz), 7.78 (d, 1H,
J = 7.7 Hz), 7.83 (br s, 1H), 8.18 (ddd, 1H, J = 1.5; 2.3;
7.9 Hz), 8.71 (dd, 1H, J = 1.5; 4.9 Hz), 8.98 (d, 1H,
J = 2.3 Hz); dC (75 MHz, CDCl3) 108.4 (C), 115.0 (C),
122.9 (q, CH, J = 4 Hz), 123.9 (q, CF3, J = 273 Hz),
124.0 (CH), 125.8 (q, CH, J = 4 Hz), 126.9 (CH), 129.3
(C), 130.1 (CH), 132.0 (q, C, J = 33 Hz), 132.9 (CH),
134.7 (CH), 141.0 (C), 143.7 (C), 148.4 (CH), 149.1 (C),
151.0 (CH) ppm; m/z 330 (M+, 100).
5.1.2.15. 2-(20-Pyridyl)-3-methoxythiophene (26). This
was prepared in 40% yield according to method C. Yel-
low oil; Anal. found: C 62.70, H 4.72, N 7.10%, calcd for