3914
M. V. Ramana Reddy et al. / Bioorg. Med. Chem. 16 (2008) 3907–3916
for C12H7F3N2O3: C, 50.71; H, 2.48; N, 9.86. Found: C,
51.09; H, 2.70; N, 10.11.
calcd for C18H14ClF3N4O2S: C, 48.82; H, 3.19; N, 12.65.
Found: C, 48.49; H, 3.09; N, 12.45.
5.3.2.11. 1,1,1-Trifluoro-4-(5-carboxy-1H-indol-3-yl)-
but-3-en-2-one (3k). Yield 40%; mp 264–266 ꢂC; 1H
NMR (CDCl3) d 6.79 (d, J = 16.0, 1H), 7.25–8.40 (m,
4H), 8.01 (d, J = 15.5, 1H), 8.40 (bs, 1H, OH). Anal.
calcd for C13H8F3NO3: C, 55.13; H, 2.85; N, 4.95.
Found: C, 54.89; H, 2.33; N, 4.49.
5.3.3.4. 4-[5-(6-Fluoro-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5d). Yield
60%; mp 194–196 ꢂC; H NMR (DMSO-d6) d 2.59 (dd,
J = 8.5 Hz, 1H), 3.38 (dd, J = 8.5 Hz, 1H), 5.59 (dd,
J = 8.0 Hz,, 1H), 6.35–7.20 (m, 8H), 10.75 (bs, 1H). Anal.
calcd for C18H14F4N4O2S: C, 50.70; H, 3.30; N, 13.14.
Found: C, 50.22; H, 2.88; N, 12.54.
1
5.3.2.12. 1,1,1-Trifluoro-4-(7-nitro-1H-indol-3-yl)-but-
1
3-en-2-one (3l). Yield 55%; mp 228–230 ꢂC; H NMR
5.3.3.5. 4-[5-(6-Chloro-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5e). Yield
62%; mp 96–98 ꢂC; H NMR (DMSO-d6) d 3.09 (dd,
J = 8.5 Hz, 1H), 3.90 (dd, J = 8.5 Hz, 1H), 6.11 (dd,
J = 8.0 Hz, 1H), 7.03–8.12 (m, 8H), 11.29 (bs, 1H). Anal.
Calcd for C18H14ClF3N4O2S: C, 48.82; H, 3.19; N, 12.65.
Found: C, 48.44; H, 2.86; N, 12.24.
(CDCl3) d 6.98 (d, J = 16.0, 1H), 7.36–8.22 (m, 4H),
8.18 (d, J = 16.5, 1H). Anal. calcd for C12H7F3N2O3: C,
50.71; H, 2.48; N, 9.86. Found: C, 50.19; H, 2.21; N, 9.11.
1
5.3.2.13. 1,1,1-Trifluoro-4-(4-methoxy-1H-indol-3-yl)-
but-3-en-2-one (3m). Yield 60%; mp 188–192 ꢂC; 1H
NMR (CDCl3) d 3.93 (s, 3H), 7.16 (d, J = 16.0, 1H),
6.61–7.64 (m, 4H), 8.50 (d, J = 15.7, 1H). Anal. calcd
for C13H10F3NO2: C, 58.00; H, 3.74; N, 5.20. Found:
C, 57.59; H, 3.41; N, 5.01.
5.3.3.6. 4-[5-(7-Chloro-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5f). Yield
1
55%; mp 166–168 ꢂC; H NMR (DMSO-d6) d 3.03 (dd,
J = 8.5 Hz, 1H), 3.71 (dd, J = 8.5 Hz, 1H), 5.91 (dd,
J = 8.0 Hz, 1H), 6.86–7.60 (m, 8H), 8.0 (bs, 1H). Anal.
Calcd for C18H14ClF3N4O2S: C, 48.82; H, 3.19; N, 12.65.
Found: C, 48.33; H, 2.80; N, 12.31.
5.3.3. General procedure for the synthesis of substituted 4-[5-
(1H-Indol-3-yl)-3-trifluoromethyl-4,5-dihydropyrazol-1-
yl]-benzenesulfonamide (5). To a stirred solution of
substituted (E)1,1,1-trifluoro-4-(1H-indol-3-yl)-but-3-en-
2-one (3) (2.5 mmol) in ethanol (10 mL) was added (4-sul-
famylphenyl)hydrazine hydrochloride (4) (3 mmol) insmall
portions and the reaction mixture was refluxed for 8–10 h.
The progress of the reaction was monitored by TLC. After
completion, the reaction mixture was cooled to 25 ꢂC and
the solid separated out in most cases was filtered, washed
with ethanol, and dried. In some instances where solid
did not separate, the reaction mixture was poured into cold
water, extracted with ethyl acetate (2 · 100 mL), washed
with brine, dried over anhydrous Na2SO4, and evaporated
the solvent under reduced pressure. The oily product ob-
tained was triturated with 2-propanol and the solid sepa-
rated was filtered and dried. The crude products were
recrystallized from ethanol to give pure 5.
5.3.3.7. 4-[5-(5-Cyano-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5g). Yield
1
60%; mp 241–244 ꢂC; H NMR (DMSO-d6) d 3.15 (dd,
J = 8.5 Hz, 1H), 3.93 (dd, J = 8.5 Hz, 1H), 6.18 (dd,
J = 8.0 Hz, 1H), 7.09–8.11 (m, 8H), 11.73 (bs, 1H). Anal.
calcd for C19H14F3N5O2S: C, 52.65; H, 3.25; N, 16.15.
Found: C, 52.29; H, 3.39; N, 15.99.
5.3.3.8. 4-[5-(6-Bromo-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5h). Yield
1
68%; mp 112–114 ꢂC; H NMR (DMSO-d6) d 3.10 (dd,
J = 8.5 Hz, 1H), 3.90 (dd, J = 8.5 Hz, 1H), 6.12 (dd,
J = 8.0 Hz, 1H), 7.06–7.62 (m, 8H), 11.37 (bs, 1H). Anal.
calcd for C18H14BrF3N4O2S: C, 44.36; H, 2.89; N, 11.49.
Found: C, 43.34; H, 2.22; N, 10.73.
5.3.3.1. 4-[5-(1H-Indol-3-yl)-3-trifluoromethyl-4,5-dihy-
dropyrazol-1-yl]-benzenesulfonamide (5a). Yield 53%; mp
160–162 ꢂC; H NMR (CDCl3) d 3.22 (dd, J = 8.5 Hz,
1H), 3.74 (dd, J = 8.5 Hz, 1H), 4.60 (bs, 2H), 5.80 (dd,
J = 6.5 Hz, 1H), 7.08–7.69 (m, 9H), 8.19 (bs, 1H). Anal.
Calcd for C18H15F3N4O2S: C, 52.94; H, 3.70; N, 13.72.
Found: C, 53.09; H, 3.81; N, 13.90.
5.3.3.9. 4-[5-(5-Amino-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5i). Yield
50%; mp 152–156 ꢂC; H NMR (DMSO-d6) d 2.30 (bs,
2H), 2.94 (dd, J = 8.5 Hz, 1H), 3.70 (dd, J = 8.5 Hz, 1H),
6.15 (dd, J = 8.0 Hz, 1H), 6.81–8.17 (m, 8H), 11.66 (bs,
1H). Anal. calcd for C18H16F3N5O2S: C, 51.05; H, 3.80;
N, 16.53. Found: C, 50.99; H, 3.69; N, 16.33.
1
1
5.3.3.2. 4-[5-(5-Fluoro-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5b). Yield
60%; mp 193–196 ꢂC; H NMR (DMSO-d6) d 2.58 (dd,
J = 8.5 Hz, 1H), 3.41 (dd, J = 8.5 Hz, 1H), 5.95 (dd,
J = 6.5 Hz, 1H), 6.40–7.20 (m, 8H), 10.78 (bs, 1H). Anal.
Calcd for C18H14F4N4O2S: C, 50.70; H, 3.30; N, 13.14.
Found: C, 50.26; H, 3.09; N, 12.70.
5.3.3.10. 4-[5-(4-Amino-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5j). Yield
40%; mp 140–144 ꢂC; H NMR (DMSO-d6) d 2.50 (bs,
2H), 3.24 (dd, J = 8.5 Hz, 1H), 3.54 (dd, J = 8.5 Hz, 1H),
6.58 (dd, J = 8.0 Hz, 1H), 6.90–7.70 (m, 8H), 8.30 (bs,
1H). Anal. calcd for C18H16F3N5O2S: C, 51.05; H, 3.80;
N, 16.53. Found: C, 51.22; H, 3.69; N, 16.49.
1
1
5.3.3.3. 4-[5-(5-Chloro-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5c). Yield
62%; mp 163–165 ꢂC; H NMR (DMSO-d6) d 2.44 (dd,
J = 8.5 Hz, 1H), 3.23 (dd, J = 8.5 Hz, 1H), 5.46 (dd,
J = 6.5 Hz, 1H), 6.32–7.18 (m, 8H), 10.70 (bs, 1H). Anal.
5.3.3.11. 4-[5-(6-Cyano-1H-indol-3-yl)-3-trifluoromethyl-
4,5-dihydropyrazol-1-yl]-benzenesulfonamide (5k). Yield
55%; mp 222–224 ꢂC; H NMR (DMSO-d6) d 3.10 (dd,
J = 8.5 Hz, 1H), 3.74 (dd, J = 8.5 Hz, 1H), 6.40 (dd,
1
1