6118 Journal of Medicinal Chemistry, 2008, Vol. 51, No. 19
Wang et al.
5% EtOAc/hexane): Rf ) 0.20. 1H NMR (CDCl3, 200 MHz) δ
2.31 (s, 3H), 3.91 (s, 3H), 3.92 (s, 3H), 6.91 (d, J ) 8.0 Hz, 1H),
6.92 (d, J ) 5.8 Hz, 1H), 6.97 (d, J ) 1.8 Hz, 1H), 7.02 (d, J )
8.0 Hz, 2.2 Hz, 1H), 7.17 (d, J ) 5.2 Hz, 1H). MS (ESI(+)) m/z
235 [M + H]+.
4-(3-Methylthiophen-2-yl)benzene-1,2-diol (21). This compound
was obtained from 21a in presence of BBr3 according to the
procedure described for 14 in 50%. TLC (SiO2, 25% EtOAc/
hexane): Rf ) 0.33. 1H NMR (CD3OD, 500 MHz) δ 2.26 (s, 3H),
6.76 (dd, J ) 8.0 Hz, 2.0 Hz, 1H), 6.80 (d, J ) 8.5 Hz, 1H), 6.86
(d, J ) 5.5 Hz, 1H), 6.87 (d, J ) 2.0 Hz, 1H), 7.15 (d, J ) 5.0 Hz,
1H). 13C NMR (CD3OD, 125 MHz) δ 15.06, 116.53, 117.36,
121.91, 123.35, 128.12, 131.90, 133.28, 139.46, 146.10, 146.39.
HRMS(CI) m/z 206.0399 (calcd for C11H10O2S 206.0402). HPLC
purity: system A, tR 7.23 min (99.83%); system B, tR 10.59 min
(99.01%).
2-(3,4-Dimethoxyphenyl)-3-ethylthiophene (22a). This compound
was obtained from 3,4-dimethoxyphenylboronic acid and 2-bromo-
3-ethylthiophene28 according to the procedure described for 14a
in 81%. TLC (SiO2, 5% EtOAc/hexane): Rf ) 0.21. 1H NMR
(CDCl3, 200 MHz) δ 1.23 (t, J ) 7.8 Hz, 3H), 2.68 (q, J ) 7.6
Hz, 2H), 3.91 (s, 3H), 3.92 (s, 3H), 6.88-7.02 (4H), 7.20 (d, J )
5.0 Hz, 1H). MS (ESI(+)) m/z 249 [M + H]+.
146.35. MS (ESI(+)) m/z 249 [M + H]+. HRMS(CI) m/z 248.0858
(calcd for C14H16O2S 248.0871). HPLC purity: system A, tR 10.25
min (99.96%); system B, tR 12.57 min (99.01%).
2-(2-(3,4-Dimethoxyphenyl)thiophen-3-yl)ethanol (25a). This com-
pound was obtained from 3,4-dimethoxyphenylboronic acid and
2-(2-bromothiophen-3-yl)ethanol28 according to the procedure
described for 14a in 50%. TLC (SiO2, 30% EtOAc/hexane): Rf )
0.15. 1H NMR (CDCl3, 200 MHz) δ 2.95 (t, J ) 6.2 Hz, 3H), 3.84
(t, J ) 6.6 Hz, 2H), 3.91 (s, 3H), 3.92 (s, 3H), 6.93 (m, 1H), 7.00(m,
2H), 7.25 (m, 2H).
4-(3-(2-Bromoethyl)thiophen-2-yl)benzene-1,2-diol (25). This
compound was obtained from 25a in presence of BBr3 according
to the procedure described for 14 in 38%. TLC (SiO2, 25% EtOAc/
1
hexane): Rf ) 0.30. H NMR (CD3OD, 500 MHz) δ 3.17 (t, J )
7.5 Hz, 2H), 3.53 (t, J ) 7.5 Hz, 2H), 6.74 (dd, J ) 8.5 Hz, 2.0
Hz, 1H), 6.81 (d, J ) 8.5 Hz, 1H), 6.84 (d, J ) 2.0 Hz, 1H), 6.99
(d, J ) 5.0 Hz, 1H), 7.23 (d, J ) 5.0 Hz, 1H). 13C NMR (CD3OD,
125 MHz) δ 32.78, 33.50, 116.65, 117.71, 122.27, 124.32, 127.23,
130.00, 135.43, 141.62, 146.56, 146.64. MS (ESI(+)) m/z 299/
301 [M + H]+. HRMS(CI) m/z 297.9653 (calcd for C12H11BrO2S
297.9663). HPLC purity: system A, tR 8.54 min (99.33%); system
B, tR 11.42 min (98.10%).
3-(3,4-Dimethoxyphenyl)thiophene (26a). This compound was
obtained from commercial available compound 3,4-dimethoxyphe-
nylboronic acid and 3-bromothiophene according to the procedure
described for 14a in 64%. TLC (SiO2, 5% EtOAc/hexane): Rf )
4-(3-Ethylthiophen-2-yl)benzene-1,2-diol (22). This compound
was obtained from 22a in presence of BBr3 according to the
procedure described for 14 in 71%. TLC (SiO2, 25% EtOAc/
1
1
hexane): Rf ) 0.33. H NMR (CD3OD, 500 MHz) δ 1.18 (t, J )
0.20. H NMR (CDCl3, 200 MHz) δ 3.91 (s, 3H), 3.94 (s, 3H),
7.5 Hz, 3H), 2.64 (q, J ) 7.5 Hz, 2H), 6.73 (dd, J ) 8.0 Hz, 2.5
Hz, 1H), 6.81 (d, J ) 8.0 Hz, 1H), 6.86 (d, J ) 2.5 Hz, 1H), 6.93
(d, J ) 5.0 Hz, 1H), 7.16 (d, J ) 5.0 Hz, 1H). 13C NMR (CD3OD,
125 MHz) δ 16.01, 22.95, 116.50, 117.61, 122.16, 123.82, 127.99,
130.00, 139.09, 140.29, 146.15, 146.31. MS (ESI(-)) m/z 219 [M
- H]-. HRMS(CI) m/z 220.0555 (calcd for C12H12O2S 220.0558).
HPLC purity: system A, tR 8.71 min (99.72%); system B, tR 11.30
min (99.39%).
6.90 (d, J ) 8.4 Hz, 1H), 7.10 (d, J ) 1.8 Hz, 1H), 7.15 (dd, J )
8.4 Hz, 1.8 Hz, 1H), 7.32-7.38 (3H). MS (ESI(+)) m/z 221 [M +
H]+.
4-(Thiophen-3-yl)benzene-1,2-diol (26). This compound was
obtained from 26a in presence of BBr3 according to the procedure
described for 14 in 57%. TLC (SiO2, 25% EtOAc/hexane): Rf )
1
0.32. H NMR (CD3OD, 500 MHz) δ 6.77 (d, J ) 8.0 Hz, 1H),
6.97 (dd, J ) 8.0 Hz, 2.5 Hz, 1H), 7.06 (d, J ) 2.5 Hz, 1H), 7.32
(dd, J ) 5.0 Hz, 1.0 Hz, 1H), 7.37 (dd, J ) 3.0 Hz, 1 Hz, 1H),
7.39 (dd, J ) 5.0 Hz, 3.0 Hz, 1H). 13C NMR (CD3OD, 125 MHz)
δ 114.68, 116.79, 119.16, 119.37, 126.86, 127.17, 129.74, 143.87,
145.90, 146.62. MS (ESI(+)) m/z 193 [M + H]+. HRMS (EI) m/z
192.0238 (calcd for C10H8O2S 192.0245). HPLC purity: system A,
tR 6.07 min (97.24%); system B, tR 9.59 min (98.16%).
2-(3,4-Dimethoxyphenyl)-3-propylthiopene (23a). This com-
pound was obtained from 3,4-dimethoxyphenylboronic acid and
2-bromo-3-propylthiophene28 according to the procedure described
1
for 14a in 70%. TLC (SiO2, 5% EtOAc/hexane): Rf ) 0.22. H
NMR (CDCl3, 200 MHz) δ 0.92 (t, J ) 7.2 Hz, 3H), 1.65 (m,
2H), 2.62 (t, J ) 7.8 Hz, 2H), 3.90 (s, 3H), 3.92 (s, 3H), 6.82-7.01
(4H), 7.19 (d, J ) 5.4 Hz, 1H). MS (ESI(+)) m/z 263 [M + H]+.
4-(3-Propylthiophen-2-yl)benzene-1,2-diol (23). This compound
was obtained from 23a in presence of BBr3 according to the
procedure described for 14 in 13%. TLC (SiO2, 25% EtOAc/
3-(3,4-Dimethoxyphenyl)-2,5-dimethylthiophene (27a). This com-
pound was obtained from 3,4-dimethylphenylboronic acid and
3-iodo-2,5-dimethylthiophene-2,5-dimethylthiophene29 according to
the procedure described for 14a in 90%. TLC (SiO2, 5% EtOAc/
1
1
hexane): Rf ) 0.33. H NMR (CD3OD, 500 MHz) δ 0.89 (t, J )
hexane): Rf ) 0.28. H NMR (CDCl3, 200 MHz) δ 2.43 (s, 3H),
7.5 Hz, 3H), 1.59 (m, 2H), 2.60 (t, J ) 7.5 Hz, 2H), 6.72 (d, J )
8.0 Hz, 1H), 6.80 (d, J ) 8.0 Hz, 1H), 6.85 (s, 1H), 6.91 (d, J )
5.0 Hz, 1H), 7.17 (d, J ) 4.5 Hz, 1H). 13C NMR (CD3OD, 125
MHz) δ 14.39, 25.32, 31.81, 116.47, 117.77, 122.29, 123.69,
128.07, 130.38, 138.77, 139.64, 146.19, 146.33. MS (ESI(+)) m/z
235 [M + H]+. HRMS(CI) m/z 234.0705 (calcd for C13H14O2S
234.0715). HPLC purity: system A, tR 9.19 min (99.77%); system
B, tR 11.94 min (99.60%).
2.44 (s, 3H), 3.90 (s, 3H), 3.91 (s, 3H), 6.68 (1H), 6.89-6.91 (3H).
MS (ESI(+)) m/z 249 [M + H]+.
4-(2,5-Dimethylthiophen-3-yl)benzene-1,2-diol (27). This com-
pound was obtained from 27a in presence of BBr3 according to
the procedure described for 14 in 90%. TLC (SiO2, 25% EtOAc/
hexane): Rf ) 0.34. 1H NMR (CD3OD, 500 MHz) δ 2.36 (s, 3H),
2.37 (s, 3H), 6.59 (s, 1H), 6.66 (m, 1H), 6.78 (m, 2H). 13C NMR
(CD3OD, 125 MHz) δ 14.31, 15.15, 116.38, 116.88, 121.37, 127.55,
128.49, 130.53, 136.15, 139.75, 145.26, 146.14. MS (ESI(+)) m/z
221 [M + H]+. HRMS(CI) m/z 220.0551 (calcd for C12H12O2S
220.0558). HPLC purity: system A, tR 9.61 min (98.52%); system
B, tR 12.31 min (99.55%).
3-Butyl-2-(3,4-dimethoxyphenyl)thiophene (24a). This compound
was obtained from 3,4-dimethoxyphenylboronic acid and 2-bromo-
3-butylthiophene28 according to the procedure described for 14a
in 72%. TLC (SiO2, 5% EtOAc/Hexane): Rf ) 0.19. 1H NMR
(CDCl3, 200 MHz) δ 0.68 (t, J ) 7.4 Hz, 3H), 1.13 (m, 2H), 1.39
(m, 2H), 2.45 (t, J ) 7.4 Hz, 2H), 3.70 (s, 3H), 3.71 (s, 3H),
6.68-6.77 (4H), 6.98 (d, J ) 5.4 Hz, 1H). MS (ESI(+)) m/z 277
[M + H]+.
3-(3,4-Bis(benzyloxy)phenyl)-2,5-dichlorothiophene (28a). This
compound was obtained from 3,4-bis(benzyloxy)phenylboronic acid
and 3-bromo-2,5-dichlorothiophene according to the procedure
described for 14a in 68%. TLC (SiO2, 5% EtOAc/hexane): Rf )
0.51. 1H NMR (CDCl3, 500 MHz) δ 5.198 (s, 2H), 5.202 (s, 2H),
6.81 (s, 1H), 6.97 (d, J ) 8.0 Hz, 1H), 7.01 (dd, J ) 8.0 Hz, 2.0
Hz, 1H), 7.12 (d, J ) 2.0 Hz, 1H), 7.32 (m, 2H), 7.37 (m, 4H),
7.45 (m, 4H). MS (ESI(+)) m/z 463 [M + Na]+.
4-(3-Butylthiophen-2-yl)benzene-1,2-diol (24). This compound
was obtained from 24a in presence of BBr3 according to the
procedure described for 14 in 15%. TLC (SiO2, 25% EtOAc/
1
hexane): Rf ) 0.33. H NMR (CD3OD, 500 MHz) δ 0.87 (t, J )
7.5 Hz, 3H), 1.30 (m, 2H), 1.55 (m, 2H), 2.62 (t, J ) 7.0 Hz, 2H),
6.71 (d, J ) 8.0 Hz, 1 H), 6.79 (d, J ) 8.0 Hz, 1H), 6.83 (d, J )
2.0 Hz, 1H), 6.91 (d, J ) 5.0 Hz, 1H), 7.61 (d, J ) 3.5 Hz, 1H).
13C NMR (CD3OD, 125 MHz) δ 14.31, 23.60, 29.38, 34.45, 116.47,
117.78, 122.29, 123.72, 128.06, 130.37, 138.93, 139.53, 146.20,
4-(2,5-dichlorothiophen-3-yl)benzene-1,2-diol (28). This com-
pound was obtained from 28a in presence of BCl3 according to
the procedure described for 14 in 57%. TLC (SiO2, 25% EtOAc/
hexane): Rf ) 0.37. H NMR (CD3OD, 500 MHz) δ 6.81 (d, J )
8.0 Hz, 1H), 6.86 (dd, J ) 8.0 Hz, 2.0 Hz, 1H), 6.97 (s, 1H), 6.99
1