May-Jun 2006
Convenient Synthesis of Novel 5-Substituted 3-Methylisoxazole-4-sulfonamides
669
N-Benzyl-5-[(E)-2-(dimethylamino)vinyl]-3-methyl-N-(2-phenyl-
ethyl)isoxazole-4-sulfonamide (6a).
1H), 7.25-7.35 (m, 4H), 7.45 (d, 1H, J = 13.7 Hz); hrms: m/z
373.4712 (M+); hrms calcd: 373.4805.
Anal. Calcd. for C19H23N3O3S: C, 61.10; H, 6.21; N, 11.25.
Found: C, 61.23; H, 6.03; N, 11.43.
This compound was obtained as colorless crystals (water),
yield 70% (29.79 g); mp 178-180°; 1H nmr: ꢀ 2.23 (s, 3H), 2.66
(t, 2H, J = 8.2 Hz), 3.03 (br s, 6H), 3.23 (t, 2H, J = 8.2 Hz), 4.33
(s, 2H), 5.44 (d, 1H, J = 13.7 Hz), 6.95 (d, 2H, J = 7.3 Hz), 7.11
(t, 1H, J = 7.4 Hz), 7.17 (t, 2H, J = 7.4 Hz), 7.27-7.31 (m, 3H),
7.33 (t, 2H, J = 8.2 Hz), 7.45 (d, 1H, J = 13.7 Hz); hrms: m/z
425.5751 (M+); hrms calcd: 425.5589.
N,N-Dimethyl-N-[(E)-2-(3-methyl-4-{[4-(4-nitrophenyl)piper-
azin-1-yl]sulfonyl}isoxazol-5-yl)vinyl]amine (6g).
This compound was obtained as colorless crystals (water),
yield 69% (29.08 g); mp 167-169°; 1H nmr: ꢀ 2.29 (s, 3H), 3.05
(br s, 6H), 3.18 (m, 4H), 3.55 (m, 4H), 5.35 (d, 1H, J = 13.7 Hz),
6.94 (d, 2H, J = 9.1 Hz), 7.47 (d, 1H, J = 13.7 Hz), 8.05 (d, 2H, J
= 9.1 Hz); hrms: m/z 421.4776 (M+); hrms calcd: 421.4842.
Anal. Calcd. for C18H23N5O5S: C, 51.30; H, 5.50; N, 16.62.
Found: C, 51.15; H, 5.72; N, 16.44.
Anal. Calcd. for C23H27N3O3S: C, 56.23; H, 5.92%N, 10.77.
Found: C, 56.42; H, 6.12; N, 10.58.
N,N-Dimethyl-N-{(E)-2-[3-methyl-4-(pyrrolidin-1-ylsulfon-yl)-
isoxazol-5-yl]vinyl}amine (6b).
This compound was obtained as colorless crystals (water),
yield 85% (24.26 g); mp 193-195°; 1H nmr: ꢀ 1.87 (br t, 4H, J =
7.4 Hz), 2.27 (s, 3H), 3.03 (br s, 6H), 3.18 (t, 4H, J = 7.4 Hz),
5.38 (d, 1H, J = 13.7 Hz), 7.43 (d, 1H, J = 13.7 Hz); hrms: m/z
285.3651 (M+); hrms calcd: 285.3712.
General Procedure for the Synthesis of Compounds (7a-f).
The experimental procedure was identical to that described
for the synthesis of (6a-g), except that 2 molar equivalents of
(dimethoxymethyl)-N,N-dimethylamine were used.
Anal. Calcd. for C12H19N3O3S: C, 50.51; H, 6.71; N, 14.72.
Found: C, 50.31; H, 6.66; N, 14.81.
N-Benzhydryl-5-[(E)-2-(dimethylamino)vinyl]-N,3-dimethyl-
isoxazole-4-sulfonamide (7a).
This compound was obtained as colorless crystals (water),
yield 77% (31.69 g); mp 178-181°; 1H nmr: ꢀ 2.07 (s, 3H), 2.63
(s, 3H), 2.98 (br s, 6H), 5.34 (d, 1H, J = 13.7 Hz), 6.33 (s, 1H),
7.13 (d, 4H, J = 7.4 Hz), 7.24-7.34 (m, 6H), 7.42 (d, 1H, J = 13.7
Hz); hrms: m/z 411.5201 (M+); hrms calcd: 411.5331.
Anal. Calcd. for C22H25N3O3S: C, 64.21; H, 6.12; N, 10.21.
Found: C, 64.12; H, 6.33; N, 10.26.
N-{(E)-2-[4-(2,3-dihydro-1H-indol-1-ylsulfonyl)-3-methyl-isox-
azol-5-yl]vinyl}-N,N-dimethylamine (6c).
This compound was obtained as colorless crystals (water),
yield 65% (21.67 g); mp 200-201°; 1H nmr: ꢀ 2.04 (s, 3H), 2.98
(t, 2H, J = 8.3 Hz), 3.00 (br s, 6H), 3.88 (t, 2H, J = 8.3 Hz), 5.30
(d, 1H, J = 13.7 Hz), 6.98 (t, 1H, J = 7.3 Hz), 7.12 (t, 2H, J = 7.3
Hz), 7.43 (d, 1H, J = 13.7 Hz), 7.46 (d, 1H, J = 7.3 Hz); hrms:
m/z 333.3991 (M+); hrms calcd: 333.4112.
N-[2-(4-Chlorophenyl)ethyl]-5-[(E)-2-(dimethylamino)vinyl]-
N,3-dimethylisoxazole-4-sulfonamide (7b).
Anal. Calcd. for C16H19N3O3S: C, 53.90; H, 6.13; N, 12.16%
Found: C, 53.77; H, 6.01; N, 12.25.
This compound was obtained as colorless crystals (water),
yield 80% (30.71 g); mp 180-182°; 1H nmr: ꢀ 2.19 (s, 3H), 2.74
(s, 3H), 2.84 (t, 2H, J = 7.4 Hz), 3.03 (br s, 6H), 3.25 (t, 2H, J =
7.4 Hz), 5.33 (d, H, J = 13.7 Hz), 7.17 (d, 2H, J = 8.3 Hz), 7.24
(d, 2H, J = 8.3 Hz), 7.43 (d, 1H, J = 13.7 Hz); hrms: m/z
383.8901 (M+); hrms calcd: 383.9681.
N-{(E)-2-[4-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylsulfonyl)-3-methyl-
isoxazol-5-yl]vinyl}-N,N-dimethylamine (6d).
This compound was obtained as colorless crystals (water),
yield 72% (25.73 g); mp 177-180°; 1H nmr: ꢀ 1.72 (t, 4H, J = 5.5
Hz), 2.25 (s, 3H), 3.03 (br s, 6H,), 3.13 (t, 4H, J = 5.5 Hz), 3.89
(s, 4H), 5.31 (d, 1H, J = 13.7 Hz), 7.45 (d, 1H, J = 13.7 Hz);
hrms: m/z 357.4212 (M+); hrms calcd: 357.4342.
Anal. Calcd. for C17H22ClN3O3S: C, 53.19; H, 5.78; Cl, 9.23;
N, 10.95. Found: C, 53.22; H, 5.51; N, 10.88.
N-(1,3-Benzodioxol-5-ylmethyl)-5-[(E)-2-(dimethylamino)-vinyl]-
N,3-dimethylisoxazole-4-sulfonamide (7c).
Anal. Calcd. for C15H23N3O5S: C, 50.41; H, 6.49; N, 11.76.
Found: C, 50.21; H, 6.64; N, 11.71.
This compound was obtained as colorless crystals (water),
yield 78% (29.6 g); mp 197-198°; 1H nmr: ꢀ 2.29 (s, 3H), 2.57
(s, 3H), 3.04 (br s, 6H), 4.05 (s, 2H), 5.37 (d, H, J = 13.7 Hz),
5.97 (s, 2H), 6.70-6.76 (m, 2H), 6.81 (s, 1H), 7.47 (d, H, J =
13.7 Hz); hrms: m/z 379.4317 (M+); hrms calcd: 379.4443.
Anal. Calcd. for C17H21N3O5S: C, 53.81; H, 5.58; N, 11.07.
Found: C, 53.73; H, 5.61; N, 11.11.
N-{(E)-2-[4-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)-3-methyl-
isoxazol-5-yl]vinyl}-N,N-dimethylamine (6e).
This compound was obtained as colorless crystals (water),
yield 81% (28.14 g); mp 182-185°; 1H nmr: ꢀ 2.28 (s, 3H), 2.93
(t, 2H, J = 5.5 Hz), 3.06 (s, 6H,), 3.39 (t, 2H, J = 5.5 Hz), 4.27
(s, 2H), 5.41 (d, 1H, J = 13.7 Hz), 7.05-7.15 (m, 4H), 7.46 (d, H,
J = 13.7 Hz); hrms: m/z 347.4321 (M+); hrms calcd: 347.4421.
Anal. Calcd. for C17H21N3O3S: C, 58.77; H, 6.09; N, 12.09.
Found: C, 58.56; H, 5.87; N, 12.24.
5-[(E)-2-(dimethylamino)vinyl]-N,3-dimethyl-N-(4-methyl-phenyl)-
isoxazole-4-sulfonamide (7d).
This compound was obtained as colorless crystals (ethanol),
yield 68% (22.81 g); mp 176-178°; 1H nmr: ꢀ 1.76 (s, 3H), 2.36
(s, 3H), 2.92 (br s, 6H), 3.14 (s, 3H), 4.94 (d, 1H, J = 13.7 Hz),
7.07-7.13 (m, 4H), 7.34 (d, 1H, J = 13.7 Hz); hrms: m/z
335.4218 (M+); hrms calcd: 335.4332.
Dimethyl-{2-[3-methyl-4-(4-phenyl-3,6-dihydro-2H-pyridine-1-
sulfonyl)-isoxazol-5-yl]-vinyl}-amine (6f).
This compound was obtained as colorless crystals (water),
yield 77% (28.76 g); mp 145-147°; 1H nmr: ꢀ 2.30 (s, 3H), 2.60-
2.65 (m, 2H), 3.06 (br s, 6H), 3.36 (t, 2H, J = 5.5 Hz), 3.76-3.80
(m, 2H), 5.41 (d, 1H, J = 13.7 Hz), 6.04 (m, 1H), 7.18-7.23 (m,
Anal. Calcd. for C16H21N3O3S: C, 57.29; H, 6.31; N, 12.53.
Found: C, 57.33; H, 6.13; N, 12.38.