222 J ournal of Medicinal Chemistry, 2000, Vol. 43, No. 2
Puig et al.
gave 1.40 g (44%) of 11: mp 211-213 °C; 1H NMR (DMSO) δ
7.81 (s, 1H), 7.76 (d, J ) 8.5 Hz, 2H), 7.40 (s, 2H), 7.38-7.34
(m, 4H), 7.30 (d, J ) 8.5 Hz, 2H). Anal. (C15H11FN2O4S) C, H,
N, S.
3-[2-Oxo-4-(4-su lfa m oylp h en yl)-2,3-d ih yd r ooxa zol-3-yl]-
ben zoic a cid (21) was prepared according to method E
starting from 51 (1.95 g). Purification by flash chromatogra-
phy, eluting with AcOH/CH2Cl2/EtOAc/MeOH (1:78:10:5), gave
1
0.83 g (66%) of 21: mp 253 °C; H NMR (DMSO) δ 12.87 (br,
4-[3-(2-Ch lor oph en yl)-2-oxo-2,3-dih ydr ooxazol-4-yl]ben -
zen esu lfon a m id e (12) was prepared according to method E
starting from 42 (8.50 g). Recrystallization from EtOAc gave
1.97 g (30%) of 12: mp 169 °C; 1H NMR (DMSO) δ 7.90 (s,
1H), 7.74 (d, J ) 8.5 Hz, 2H), 7.71-7.63 (m, 2H), 7.55-7.50
1H), 7.97 (d, J ) 8.5 Hz, 1H), 7.91 (s, 1H), 7.86 (s, 1H), 7.68
(d, J ) 8.5 Hz, 2H), 7.57 (t, J ) 8.5 Hz, 1H), 7.45 (d, J ) 8.5
Hz, 1H), 7.40 (s, 2H), 7.31 (d, J ) 8.5 Hz, 2H). Anal.
(C16H12N2O6S) H, N, S; C: calcd, 53.33; found, 53.92.
4-[2-Oxo-4-(4-su lfa m oylp h en yl)-2,3-d ih yd r ooxa zol-3-yl]-
ben zoic a cid (22) was prepared according to method E
starting from 52 (1.63 g). Purification by flash chromatogra-
phy, eluting with AcOH/CH2Cl2/EtOAc/MeOH (1:78:10:5), gave
(m, 2H), 7.39 (s, 2H), 7.29 (d, J ) 8.5 Hz, 2H). Anal. (C15H11
ClN2O4S) C, H, N, S.
-
4-[3-(3-Ch lor oph en yl)-2-oxo-2,3-dih ydr ooxazol-4-yl]ben -
zen esu lfon a m id e (13) was prepared according to method E
starting from 43 (2.30 g). Purification by flash chromatogra-
phy, eluting with CH2Cl2/MeOH (95:5), gave 0.80 g (53%) of
13: mp 176-177 °C; 1H NMR (DMSO) δ 7.83 (s, 1H), 7.78 (d,
J ) 8.5 Hz, 2H), 7.53 (m, 1H), 7.49 (m, 1H), 7.46 (s, 1H), 7.42
1
0.52 g (48%) of 22: mp 236 °C; H NMR (DMSO) δ 12.90 (br,
1H), 8.02 (d, J ) 8.3 Hz, 2H), 7.86 (s, 1H), 7.78 (d, J ) 8.3 Hz,
2H), 7.42, (s, 2H), 7.40 (d, J ) 8.3 Hz, 2H), 7.31 (d, J ) 8.3
Hz, 2H). Anal. (C16H12N2O6S‚0.2H2O) C, H, S; N: calcd, 7.70;
found, 7.21.
(s, 2H), 7.32 (d, J ) 8.5 Hz, 2H), 7.19 (m, 1H). Anal. (C15H11
ClN2O4S) C, H, N, S.
-
4-[3-(2,4-Diflu or op h en yl)-2-oxo-2,3-d ih yd r ooxa zol-4-yl]-
ben zen esu lfon a m id e (23) was prepared according to method
E starting from 53 (2.60 g). Recrystallization from MeOH gave
4-[3-(4-Ch lor oph en yl)-2-oxo-2,3-dih ydr ooxazol-4-yl]ben -
zen esu lfon a m id e (14) was prepared according to method E
starting from 44 (1.90 g). Recrystallization from CH3CN gave
1
0.50 g (30%) of 23: mp 190-191 °C; H NMR (CDCl3) δ 7.85
(d, J ) 8.5 Hz, 2H), 7.40 (m, 1H), 7.22 (s, 1H), 7.21 (d, J ) 8.5
Hz, 2H), 7.04-6.93 (m, 2H), 6.71 (s, 2H). Anal. (C15H10F2N2O4S)
C, H, N, S.
1
0.50 g (40%) of 14: mp 213-214 °C; H NMR (DMSO) δ 7.82
(s, 1H), 7.77 (d, J ) 8.7 Hz, 2H), 7.54 (d, J ) 8.7 Hz, 2H), 7.41
(s, 2H), 7.32 (d, J ) 8.7 Hz, 2H), 7.31 (d, J ) 8.7 Hz, 2H).
Anal. (C15H11ClN2O4S) C, H, N, S.
4-[3-(3,4-Dich lor op h en yl)-2-oxo-2,3-d ih yd r ooxa zol-4-
yl]ben zen esu lfon a m id e (24) was prepared according to
method E starting from 54 (3.40 g). Purification by flash
chromatography, eluting with CHCl3/MeOH (20:1), gave 1.49
4-[2-Oxo-3-(4-tr iflu or om eth ylph en yl)-2,3-dih ydr ooxazol-
4-yl]ben zen esu lfon a m id e (15) was prepared according to
method E starting from 45 (4.40 g). Purification by flash
chromatography, eluting with EtOAc/hexane (1:1), gave 1.65
1
g (64%) of 24: mp 157-159 °C dec; H NMR (DMSO) δ 7.83
(s, 1H), 7.80 (s, 1H), 7.74 (d, J ) 8.5 Hz, 2H), 7.71 (d, J ) 8.5
Hz, 2H), 7.41 (s, 2H), 7.31 (d, J ) 8.5 Hz, 2H), 7.22 (d, J ) 8.5
Hz, 2H). Anal. (C15H10Cl2N2O4S) C, H, N, S.
1
g (55%) of 15: mp 196 °C; H NMR (DMSO) δ 7.84 (s, 1H),
7.83 (d, J ) 8 Hz, 2H), 7.76 (d, J ) 8 Hz, 2H), 7.48 (d, J ) 8
Hz, 2H), 7.40 (s, 2H), 7.29 (d, J ) 8 Hz, 2H). Anal.
(C16H11F3N2O4S) C, H, N, S.
4-[3-(3-F lu or o-4-m et h oxyp h en yl)-2-oxo-2,3-d ih yd r o-
oxa zol-4-yl]ben zen esu lfon a m id e (25) was prepared accord-
ing to method E starting from 55 (9.78 g). Purification by flash
chromatography, eluting with AcOH/CH2Cl2/EtOAc (1:78:10),
4-[3-(2-Meth ylph en yl)-2-oxo-2,3-dih ydr ooxazol-4-yl]ben -
zen esu lfon a m id e (16) was prepared according to method E
starting from 46 (2.96 g). Purification by flash chromatogra-
phy, eluting with AcOH/CH2Cl2/EtOAc (1:78:10), gave 0.80 g
1
gave 3.60 g (55%) of 25: mp 184 °C; H NMR (DMSO) δ 7.80
(s, 1H), 7.77 (d, J ) 8 Hz, 2H), 7.40-7.35 (m, 3H), 7.32 (d, J
) 8 Hz, 2H), 7.23 (t, J ) 9.5 Hz, 1H), 7.08 (d, J ) 8.5 Hz, 1H),
3.85 (s, 3H). Anal. (C16H13FN2O5S) C, H, N, S.
1
(42%) of 16: mp 99-101 °C; H NMR (DMSO) δ 7.91(s, 1H),
7.70 (d, J ) 8 Hz, 2H), 7.42-7.20 (m, 6H), 7.40 (s, 2H), 2.14
(s, 3H). Anal. (C16H14N2O4S) C, H, N, S.
4-[3-(3-Ch lor o-4-m et h oxyp h en yl)-2-oxo-2,3-d ih yd r o-
oxa zol-4-yl]ben zen esu lfon a m id e (26) was prepared accord-
ing to method E starting from 56 (1.50 g). Purification by flash
chromatography, eluting with EtOAc/hexane (1:1), gave 0.68
4-[3-(3-Meth ylph en yl)-2-oxo-2,3-dih ydr ooxazol-4-yl]ben -
zen esu lfon a m id e (17) was prepared according to method E
starting from 47 (16.0 g). Purification by flash chromatogra-
phy, eluting with AcOH/CH2Cl2/EtOAc (1:78:10), gave 7.26 g
(70%) of 17: mp 192 °C; 1H NMR (DMSO) δ 7.82 (s, 1H), 7.74
(d, J ) 8.7 Hz, 2H), 7.40 (s, 2H), 7.32 (m, 1H), 7.29 (d, J ) 8.7
Hz, 2H), 7.23 (d, J ) 8 Hz, 1H), 7.20 (s, 1H) 7.01 (d, J ) 8 Hz,
1H), 2.31 (s, 3H). Anal. (C16H14N2O4S) C, H, N, S.
4-[3-(4-Meth ylph en yl)-2-oxo-2,3-dih ydr ooxazol-4-yl]ben -
zen esu lfon a m id e (18) was prepared according to method E
starting from 48 (2.66 g). Purification by flash chromatogra-
phy, eluting with AcOH/CH2Cl2/EtOAc (1:78:10), gave 1.00 g
(58%) of 18: mp 223 °C; 1H NMR (DMSO) δ 7.80 (s, 1H), 7.74
(d, J ) 8 Hz, 2H), 7.40 (s, 2H), 7.29 (d, J ) 8.7 Hz, 2H), 7.26
(d, J ) 8.7 Hz, 2H), 7.17 (d, J ) 8 Hz, 2H), 2.33 (s, 3H). Anal.
(C16H14N2O4S) C, H, N, S.
4-[3-(4-Eth ylp h en yl)-2-oxo-2,3-d ih yd r ooxa zol-4-yl]ben -
zen esu lfon a m id e (19) was prepared according to method E
starting from 49 (0.50 g). Purification by flash chromatogra-
phy, eluting with AcOH/CH2Cl2/EtOAc (1:78:10), gave 0.25 g
(79%) of 19: mp 199 °C; 1H NMR (DMSO) δ 7.81 (s, 1H), 7.73
(d, J ) 8 Hz, 2H), 7.39 (s, 2H), 7.30 (d, J ) 8 Hz, 4H), 7.19 (d,
J ) 8 Hz, 2H), 2.64 (q, J ) 7.5 Hz, 2H), 1.86 (t, J ) 7.5 Hz,
3H). Anal. (C16H14N2O4S) C, H, N, S.
1
g (67%) of 26: mp 194 °C; H NMR (DMSO) δ 7.80 (s, 1H),
7.76 (d, J ) 8.7 Hz, 2H), 7.55 (m, 1H), 7.40 (s, 2H), 7.32 (d, J
) 8.7 Hz, 2H), 7.22-7.20 (m, 2H), 3.88 (s, 3H). Anal. (C16H13
ClN2O5S) C, H, N, S.
-
4-(3-Cycloh exyl-2-oxo-2,3-d ih yd r ooxa zol-4-yl)ben zen e-
su lfon a m id e (27) was prepared according to method E
starting from 57 (1.50 g). Purification by flash chromatogra-
phy, eluting with EtOAc/hexane (1:1), gave 0.40 g (42%) of
1
27: mp 167-169 °C; H NMR (DMSO) δ 7.94 (d, J ) 8.5 Hz,
2H), 7.61 (d, J ) 8.5 Hz, 2H), 7.50 (s, 2H), 7.42 (s, 1H), 3.46
(m, 1H), 2.13-2.00 (m, 2H), 1.77-1.74 (m, 4H), 1.55 (m, 1H),
1.18-1.06 (m, 3H). Anal. (C15H18N2O4S) C, H, N, S.
4-[(3-Na p h t h a len -1-yl)-2-oxo-2,3-d ih yd r ooxa zol-4-yl]-
ben zen esu lfon a m id e (28) was prepared according to method
E starting from 58 (7.36 g). Purification by flash chromatog-
raphy, eluting with AcOH/CH2Cl2/EtOAc (1:78:10), gave 1.81
1
g (37%) of 28: mp 186 °C; H NMR (DMSO) δ 8.10-8.04 (m,
2H), 8.00 (s, 1H), 7.75 (m, 1H), 7.67-7.59 (m, 4H), 7.60 (d, J
) 8 Hz, 2H), 7.28 (s, 2H), 7.24 (d, J ) 8 Hz, 2H). Anal.
(C19H14N2O4S‚0.35H2O) C, H, S; N: calcd, 7.52; found, 7.02.
4-(5-Meth yl-2-oxo-3-ph en yl-2,3-dih ydr ooxazol-4-yl)ben -
zen esu lfon a m id e (29) was prepared according to method E
starting from 64 (6.46 g). Purification by flash chromatogra-
phy, eluting with AcOH/CH2Cl2/EtOAc (1:78:10), gave 2.90 g
(70%) of 29: mp 101 °C; 1H NMR (DMSO) δ 7.73 (d, J ) 6 Hz,
2H), 7.41-7.35 (m, 5H), 7.20 (d, J ) 6 Hz, 2H), 7.18 (d, J ) 7
Hz, 2H), 2.21 (s, 3H). Anal. (C16H14N2O4S) C, H, N, S.
4-[3-(4-Meth oxyp h en yl)-2-oxo-2,3-d ih yd r ooxa zol-4-yl]-
ben zen esu lfon a m id e (20) was prepared according to method
E starting from 50 (11.40 g). Purification by flash chromatog-
raphy, eluting with EtOAc/hexane (1:1), gave 1.40 g (20%) of
1
20: mp 196 °C; H NMR (CDCl3) δ 7.84 (d, J ) 8.7 Hz, 2H),
7.23 (d, J ) 8.7 Hz, 2H), 7.13 (s, 1H), 7.12 (d, J ) 9 Hz, 2H),
6.92 (d, J ) 9 Hz, 2H), 4.78 (s, 2H), 3.82 (s, 3H). Anal.
(C16H14N2O5S) H, N, S; C: calcd, 55.48; found, 56.01.
4-[3-(4-Flu or oph en yl)-5-m eth yl-2-oxo-2,3-dih ydr ooxazol-
4-yl]ben zen esu lfon a m id e (30) was prepared according to