Journal of Medicinal Chemistry
ARTICLE
recrystallization from ethanol resulted in pure product 26a. Yield, 70%; white
1H NMR (CDCl3, 300 MHz): δ 3.49 (s, 3H, OCH3), 3.51 (s, 6H, 2 ꢁ
OCH3), 3.55 (s, 3H, OCH3), 3.57 (s, 3H, OCH3), 3.95ꢀ4.16 (m, 1H,
CH), 4.22 (s, 2H, CH2), 4.85 (t, J = 9.0 Hz, 1H, NH), 5.92 (s, 2H,
ArꢀH), 6.23 (dd, J = 8.4, 2.1 Hz, 1H, ArꢀH), 6.40 (d, J = 8.1 Hz, 1H,
ArꢀH), 6.53 (d, J = 2.1 Hz, 1H, ArꢀH), 6.80 (d, J = 15.6 Hz,
1H, dCH), 7.55 (d, J = 15.6 Hz, 1H, CHd). HRMS: m/z calcd
[M + H] 534.1345; found 534.1339. Anal. (C23H26F3NO8S) C, H, N.
(E)-Methyl 2-(2-Methoxy-5-((20,40,60-trimethoxystyrylsulfonyl)-
methyl)phenylamino)-2-methylpropanoate (26g). The title com-
pound was obtained by the alkylation of (E)-20,40,60-trimethoxystyryl-4-
methoxy-3-aminobenzylsulfone 8p with methyl 2-bromo2-methylpropionate
following the procedure as described for compound 26. Yield, 60%; white solid,
mp 170ꢀ172 °C. 1H NMR (CDCl3, 500 MHz): δ 1.52 (s, 6H, 2 ꢁ CH3),
3.68 (s, 3H, OCH3), 3.81 (s, 6H, 2 ꢁ OCH3), 3.82 (s, 3H, OCH3), 3.83 (s,
3H, OCH3), 4.11 (s, 2H, CH2), 6.06 (s, 2H, ArꢀH), 6.41 (s, 1H, ArꢀH),
6.69ꢀ6.71 (m, 2H, ArꢀH), 7.02 (d, J = 15.5 Hz, 1H, dCH), 7.80 (d, J= 15.5
Hz, 1H, CHd). HRMS: m/z calcd [M + H] 494.1770; found 494.1761. Anal.
(C24H31NO8S) C, H, N.
(E)-Methyl 2-(2-Methoxy-5-((20,40,60-trimethoxystyrylsulfonyl)-
methyl)phenylamino)-2-phenylacetate (26h). The title compound
was obtained by the alkylation of (E)-20,40,60-trimethoxystyryl-4-methoxy-3-
aminobenzylsulfone 8p with methyl R-bromophenylacetate following the
procedure as described for compound 26. Yield, 63%; white solid, mp
94ꢀ96 °C. 1H NMR (CDCl3, 300 MHz): δ 3.71 (s, 3H, OCH3), 3.83 (s,
6H, 2 ꢁ OCH3),3.86(s,3H,OCH3),3.88(s,3H,OCH3), 4.06 (s, 2H, CH2),
4.99 (d, J = 6.0 Hz, 1H, CH), 5.43(d, J = 6.3 Hz, 1H, NH), 6.10 (s, 2H,
ArꢀH), 6.36 (d, J=1.8Hz,1H, ArꢀH), 6.67 (dd, J= 8.1, 1.8 Hz, 1H, ArꢀH),
6.73 (d, J = 8.1 Hz, 1H, ArꢀH), 6.99 (d, J = 15.6 Hz, 1H, dCH), 7.29ꢀ7.35
(m, 3H, ArꢀH), 7.42 (dd, J = 8.1, 1.8 Hz, 2H, ArꢀH), 7.77 (d, J = 15.6 Hz,
1H, CHd). HRMS: m/z calcd [M + H] 542.1770; found 542.1778. Anal.
(C28H31NO8S) C, H, N.
(E)-Methyl 2-(400-Fluorophenyl)-2-(2-methoxy-5-((20,40,60-
trimethoxystyrylsulfonyl)methyl)phenylamino)acetate (26i). The
title compound was obtained by the alkylation of (E)-20,40,60-trimethoxystyryl-
4-methoxy-3-aminobenzylsulfone 8p with methyl 2-bromo-2- (4-fluorophe-
nyl)acetate following the procedure as described for compound 26. Yield, 60%;
white solid, mp 152ꢀ154 °C. 1H NMR (CDCl3, 500 MHz): δ 3.72 (s, 3H,
OCH3), 3.82 (s, 6H, 2 ꢁ OCH3), 3.86 (s, 3H, OCH3), 3.88 (s, 3H, OCH3),
4.05 (s, 2H, CH2), 4.98 (d, J = 2.5 Hz, 1H, CH), 6.10 (s, 2H, ArꢀH), 6.33 (d,
J= 2.0 Hz, 1H, ArꢀH), 6.69 (dd, J= 8.5, 2.0 Hz, 1H, ArꢀH), 6.73 (d, J=8.5Hz,
1H, ArꢀH), 6.96ꢀ6.99 (m, 2H, ArꢀH), 7.00 (d, J = 15.5 Hz, 1H, dCH),
7.37ꢀ7.40 (m, 2H, ArꢀH), 7.76 (d, J = 16.0 Hz, 1H, CHd). HRMS: m/z
calcd [M + H] 560.1676; found 560.1656. Anal. (C28H30FNO8S) C, H, N.
(E)-Methyl 2-(400-Chlorophenyl)-2-(2-methoxy-5-((20,40,60-
trimethoxystyrylsulfonyl)methyl)phenylamino)acetate (26j). The
title compound was obtained by the alkylation of (E)-20,40,60-trimethoxystyryl-
4-methoxy-3-aminobenzylsulfone 8p with methyl 2-bromo-2- (4-chlorophe-
nyl)acetate following the procedure as described for compound 26. Yield, 64%;
white solid, mp 154ꢀ156 °C. 1H NMR (CDCl3, 300 MHz): δ 3.72 (s, 3H,
OCH3), 3.83 (s, 6H, 2 ꢁ OCH3), 3.86 (s, 3H, OCH3), 3.88 (s, 3H, OCH3),
4.05 (s, 2H, CH2), 4.96 (s, 1H, CH), 6.11 (s, 2H, ArꢀH), 6.31 (s, 1H, ArꢀH),
6.67ꢀ6.75 (m, 2H, ArꢀH), 6.99 (d, J = 15.6 Hz, 1H, dCH), 7.25ꢀ7.28 (m,
2H, ArꢀH), 7.54 (d, J= 8.4 Hz, 2H, ArꢀH), 7.76 (d, J= 15.6 Hz, 1H, CHd).
HRMS: m/z calcd [M + H] 576.1381; found 576.1367. Anal.
(C28H30ClNO8S) C, H, N.
(E)-Methyl 2-(400-Bromophenyl)-2-(2-methoxy-5-((20,40,
60-trimethoxystyrylsulfonyl)methyl)phenylamino)acetate
(26k). The title compound was obtained by the alkylation of (E)-
20,40,60-trimethoxystyryl-4-methoxy-3-aminobenzylsulfone 8p with
methyl 2-bromo-2- (4-bromophenyl)acetate following the procedure as
described for compound 26. Yield, 62%; white solid, mp 150ꢀ152 °C.
1H NMR (CDCl3, 400 MHz): δ 3.48 (s, 3H, OCH3), 3.59 (s, 6H, 2 ꢁ
OCH3), 3.62 (s, 3H, OCH3), 3.65 (s, 3H, OCH3), 3.81 (s, 2H, CH2),
4.71(s, 1H, CH), 5.87 (s, 2H, ArꢀH), 6.07 (d, J = 1.8 Hz, 1H, ArꢀH),
1
solid, mp 150ꢀ152 °C. H NMR (CDCl3, 300 MHz): δ 3.69 (s, 3H,
OCH3), 3.75(s, 6H, 2 ꢁ OCH3), 3.78 (s, 3H, OCH3), 3.79 (s, 3H, OCH3),
3.81 (d, J = 5.4 Hz, 2H, CH2), 4.09 (s, 2H, CH2), 4.74 (t, J = 5.4 Hz, 1H,
NH), 6.01(s, 2H, ArꢀH), 6.41 (d, J = 1.8 Hz, 1H, ArꢀH), 6.61ꢀ6.68 (m,
2H, ArꢀH), 6.97 (d, J = 15.6 Hz, 1H, dCH), 7.73 (d, J = 15.6 Hz, 1H,
CHd). HRMS: m/z calcd [M + H] 466.1457; found 466.1446. Anal.
(C22H27NO8S) C, H, N.
(E)-Methyl 2-(2-Methoxy-5-((30,40,50-trimethoxystyrylsul-
fonyl)methyl)phenylamino)acetate (26b). The title compound
was obtained by the alkylation of (E)-30,40,50-trimethoxystyryl-4-meth-
oxy-3-aminobenzylsulfone 8q with methyl 2-bromoacetate following the
procedure as described for compound 26. Yield, 63%; light brown solid,
mp 82ꢀ84 °C. 1H NMR (CDCl3, 400 MHz): δ 3.67 (s, 3H, OCH3),
3.79 (s, 3H, OCH3), 3.81 (s, 6H, 2 ꢁ OCH3), 3.82 (s, 3H, OCH3), 3.86
(d, J = 5.4 Hz, 2H, CH2), 4.14 (s, 2H, CH2), 4.53 (t, J = 5.4 Hz, 1H, NH),
6.52 (d, J = 15.5 Hz, 1H, dCH), 6.57 (s, 2H, ArꢀH), 6.62 (dd, J = 8.2,
2.1 Hz, 1H, ArꢀH), 6.67 (d, J = 8.2 Hz, 1H, ArꢀH), 6.70 (d, J = 2.1 Hz,
1H, ArꢀH), 7.24 (d, J = 15.4 Hz, 1H, CHd). HRMS: m/z calcd [M +
H] 466.1457; found 466.1465. Anal. (C22H27NO8S) C, H, N.
(E)-Ethyl 3-(2-Methoxy-5-((20,40,60-trimethoxystyrylsulfo-
nyl)methyl)phenylamino)propanoate (26c). The title com-
pound was obtained by the alkylation of (E)-20,40,60-trimethoxystyryl-
4-methoxy-3-aminobenzylsulfone 8p with ethyl 3-bromopropionate
following the procedure as described for compound 26. Yield, 59%;
light green solid, mp 72ꢀ74 °C. 1H NMR (CDCl3, 300 MHz): δ 1.26 (t,
J = 7.2 Hz, 3H, CH3), 2.58 (t, J = 6.3 Hz, 2H, CH2), 3.41 (t, J = 6.6 Hz,
2H, CH2), 3.82 (s, 9H, 3 ꢁ OCH3), 3.84 (s, 3H, OCH3), 4.04ꢀ4.10 (m,
2H, OCH2), 4.17 (s, 2H, CH2), 5.06 (t, J = 5.4 Hz, 1H, NH), 6.09 (s, 2H,
ArꢀH), 6.61ꢀ6.64 (m, 1H, ArꢀH), 6.66ꢀ6.71 (m, 2H, ArꢀH), 7.06
(d, J = 15.6 Hz, 1H, dCH), 7.84 (d, J = 15.9 Hz, 1H, CHd). HRMS: m/
z calcd [M + H] 480.1614; found 480.1647. Anal. (C23H29NO8S)
C, H, N.
(E)-Methyl 2-(2-Methoxy-5-((20,40,60-trimethoxystyrylsul-
fonyl)methyl)phenylamino)propanoate (26d). The title com-
pound was obtained by the alkylation of (E)-20,40,60-trimethoxystyryl-4-
methoxy-3-aminobenzylsulfone 8p with methyl 2-bromopropionate
following the procedure as described for compound 26. Yield, 60%;
white solid, mp 178ꢀ180 °C. 1H NMR (CDCl3, 400 MHz): δ 1.24 (d,
J = 6.9 Hz, 3H, CH3), 3.50 (s, 3H, OCH3), 3.61 (s, 6H, 2 ꢁ OCH3), 3.63
(s, 3H, OCH3), 3.64 (s, 3H, OCH3), 3.90ꢀ3,92 (m, 1H, CH), 3.94 (s,
2H, CH2), 4.52 (br s, 1H, NH), 5.88 (s, 2H, ArꢀH), 6.32 (d, J = 1.7 Hz,
1H, ArꢀH), 6.47 (dd, J = 8.1, 1.7 Hz, 1H, ArꢀH), 6.52 (d, J = 8.1 Hz,
1H, ArꢀH), 6.81 (d, J = 15.6 Hz, 1H, dCH), 7.59 (d, J = 15.6 Hz, 1H,
CHd). HRMS: m/z calcd [M + H] 480.1579; found 480.1568. Anal.
(C23H29NO8S) C, H, N.
(E)-Methyl200,200-Difluoro-2(2-methoxy-5-((20,40,60-trimethox-
ystyrylsulfonyl)methyl)phenylamino)acetate (26e). The title
compound was obtained by the alkylation of (E)-20,40,60-trimethoxys-
tyryl-4-methoxy-3-aminobenzylsulfone 8p with methyl 2-chloro-2,2-
difluoroacetate following the procedure as described for compound
1
26. Yield, 57%; white solid, mp 186ꢀ188 °C. H NMR (CDCl3, 300
MHz): δ 3.74 (s, 3H, OCH3), 3.83 (s, 6H, 2 ꢁ OCH3), 3.85 (s, 3H,
OCH3), 3.87 (s, 3H, OCH3), 4.22 (s, 2H, CH2), 6.09 (s, 2H, ArꢀH),
6.86 (d, J = 8.4 Hz, 1H, ArꢀH), 7.09 (d, J = 15.6 Hz, 1H, dCH), 7.11
(dd, J = 8.4, 2.1 Hz, 1H, ArꢀH), 7.19 (s, 1H, ArꢀH), 7.84 (d, J = 15.6
Hz, 1H, CHd), 8.08 (brs, 1H, NH). HRMS: m/z calcd [M + H]
502.1269; found 502.1284. Anal. (C22H25F2NO8S) C, H, N.
(E)-Methyl 300,300,300-Trifluoro-2-(2-methoxy-5-((20,40,60-
trimethoxystyrylsulfonyl)methyl)phenylamino)propanoate
(26f). The title compound was obtained by the alkylation of (E)-20,40,60-
trimethoxystyryl-4-methoxy-3-aminobenzylsulfone 8p with methyl
2-bromo-3,3,3-trifluoropropanoate following the procedure as de-
scribed for compound 26. Yield, 56%; white solid, mp 192ꢀ194 °C.
6272
dx.doi.org/10.1021/jm200570p |J. Med. Chem. 2011, 54, 6254–6276