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87.61, 122.89, 123.36, 124.57, 128.01, 131.56, 138.18, 145.19,
158.91, 175.31 ppm; HRMS (ESI): m/z [MꢀH]ꢀ calcd for C10H7N3OS2:
250.0103, found: 250.0102.
treated according to the general procedure given above. The
crude product was purified by column chromatography (CH2Cl2/
EtOAc 5:1) affording compound 17c as an orange solid (11 mg,
12.5%): 1H NMR (300 MHz, [D6]DMSO): d=3.84 (s, 3H), 6.79 (brs,
2H), 7.14 (dd, J=9.0 Hz, J=2.4 Hz, 1H), 7.77–7.80 ppm (m, 2H);
13C NMR (75 MHz, [D6]DMSO): d=55.53, 88.60, 105.09, 117.77,
118.04, 124.04, 130.19, 132.46, 144.86, 157.32, 159.00 ppm; HRMS
(ESI): m/z [M+H]+ calcd for C11H9N3O2S2: 280.0209, found
280.0207.
5-(3-Amino-5-bromobenzo[b]thiophen-2-yl)-1,3,4-oxadiazole-
2(3H)-thione (10b): Acyl hydrazide 9b (52 mg, 0.186 mmol) was
treated according to the general procedure given above. The
crude product was purified by column chromatography (CH2Cl2/
EtOAc 4:1) affording compound 10b as a dark-yellow solid (17 mg,
1
29%): H NMR (300 MHz, [D6]DMSO): d=6.85 (brs, 2H), 7.65 (d, J=
8.7 Hz, 1H), 7.91 (d, J=8.7 Hz, 1H), 8.47 ppm (s, 1H); 13C NMR
(75 MHz, [D6]DMSO): d=89.24, 117.70, 125.29, 125.35, 130.36,
133.16, 137.00, 143.95, 158.46, 175.25 ppm; HRMS (ESI): m/z
[MꢀH]ꢀ calcd for C10H6BrN3OS2: 325.9063, found: 325.9061.
5-(3-Amino-6-chlorobenzo[b]thiophen-2-yl)-1,3,4-oxadiazole-
2(3H)-thione (12): Acyl hydrazide 11 (95 mg, 0.393 mmol) was
treated according to the general procedure given above. The
crude product was purified by flash chromatography (cyclohexane/
EtOAc 2:1) affording compound 12 as a pale-brown solid (25 mg,
22%): 1H NMR (300 MHz, [D6]DMSO): d=6.87 (brs, 2H), 7.50 (dd,
J=8.7 Hz, J=1.5 Hz, 1H), 8.12 (brs, 1H), 8.17 ppm (d, J=8.7 Hz,
1H); 13C NMR (75 MHz, [D6]DMSO): d=88.30, 122.81, 124.15,
125.01, 130.25, 132.72, 139.41, 144.42, 158.57, 175.10 ppm; HRMS
(ESI): m/z [MꢀH]ꢀ calcd for C10H6ClN3OS2: 281.9568, found:
281.9570.
5-(3-Amino-5-(trifluoromethoxy)benzo[b]thiophen-2-yl)-1,3,4-ox-
adiazole-2(3H)-thione (17d): Acyl hydrazide 16d (144 mg,
0.469 mmol) was treated according to the general procedure given
above. The crude product was purified by column chromatography
(CH2Cl2/MeOH 100:2) affording compound 17d as a yellow solid
(43 mg, 27%): 1H NMR (300 MHz, [D6]DMSO): d=6.90 (brs, 2H),
7.51 (d, J=8.7 Hz, 1H), 8.07 (d, J=8.7 Hz, 1H), 8.28 ppm (s, 1H);
1
13C NMR (150 MHz, [D6]DMSO): d=89.99, 115.18, 120.18 (q, JC-F
=
256 Hz), 121.24, 125.24, 132.35, 136.82, 144.29, 145.85, 158.50,
175.18 ppm; 19F NMR (470 MHz, [D6]DMSO): d=ꢀ56.98 ppm; HRMS
(ESI): m/z [MꢀH]ꢀ calcd for C11H6F3N3O2S2: 331.9781, found
331.9778.
5-(3-Amino-7-(trifluoromethyl)benzo[b]thiophen-2-yl)-1,3,4-oxa-
diazole-2(3H)-thione (17e): Acyl hydrazide 16e (104 mg,
0.378 mmol) was treated according to the general procedure given
above. The crude product was purified by column chromatography
(CH2Cl2/EtOAc 4:1) affording compound 17e as a yellow solid
(26 mg, 22%): 1H NMR (300 MHz, [D6]DMSO): d=6.99 (brs, 2H),
7.68 (t, J=7.8 Hz, 1H), 7.93 (d, J=7.5 Hz, 1H), 8.49 ppm (d, J=
5-(3-Amino-5-nitrobenzo[b]thiophen-2-yl)-1,3,4-oxadiazole-
2(3H)-thione (15): Acyl hydrazide 14 (98 mg, 0.388 mmol) was
treated according to the general procedure given above. The
crude product was purified by column chromatography (CH2Cl2/
MeOH 100:0!96:4) affording compound 15 as a brown-red solid
(60 mg, 53%): 1H NMR (300 MHz, [D6]DMSO): d=7.11 (brs, 2H),
8.20 (d, J=9.0 Hz, 1H), 8.28 (dd, J=9.0 Hz, J=2.1 Hz, 1H),
9.24 ppm (d, J=2.4 Hz, 1H); 13C NMR (75 MHz, [D6]DMSO): d=
90.33, 119.08, 121.58, 124.69, 131.58, 144.25, 145.10, 145.17, 158.20,
175.59 ppm; HRMS (ESI): m/z [MꢀH]ꢀ calcd for C10H6N4O3S2:
292.9808, found 292.9808.
2
8.4 Hz, 1H); 13C NMR (150 MHz, [D6]DMSO): d=88.47, 123.39 (q, JC-
1
3
F =33 Hz), 123.92 (q, JC-F =273 Hz), 124.96, 125.74 (q, JC-F =3.6 Hz),
127.11, 133.43, 133.94, 144.39, 158.35, 174.67 ppm; 19F NMR
(470 MHz, [D6]DMSO): d=ꢀ61.75 ppm; HRMS (ESI): m/z [MꢀH]ꢀ
calcd for C11H6F3N3OS2: 315.9832, found 315.9825.
5-(3-Amino-5-(trifluoromethyl)benzo[b]thiophen-2-yl)-1,3,4-oxa-
diazole-2(3H)-thione (17f): Acyl hydrazide 16 f (110 mg,
0.400 mmol) was treated according to the general procedure given
above. The crude product was purified by column chromatography
(CH2Cl2/MeOH 100:0!99:1) affording compound 17 f as a yellow
solid (39 mg, 31%): 1H NMR (300 MHz, [D6]DMSO): d=6.99 (brs.,
2H), 7.79 (d, J=8.4 Hz, 1H), 8.19 (d, J=8.4 Hz, 1H), 8.68 ppm (s,
1H); 13C NMR (150 MHz, [D6]DMSO): d=89.65, 120.29, 123.40,
124.52, 124.53 (q, 1JC-F =272 Hz), 125.41 (q, 2JC-F =32 Hz), 131.34,
141.67, 144.47, 158.41, 175.37 ppm; 19F NMR (470 MHz, [D6]DMSO):
d=ꢀ60.11 ppm; HRMS (ESI): m/z [MꢀH]ꢀ calcd for C11H6F3N3OS2:
315.9832, found 315.9842.
5-(3-Amino-4-methoxybenzo[b]thiophen-2-yl)-1,3,4-oxadiazole-
2(3H)-thione (17a): Acyl hydrazide 16a (33 mg, 0.139 mmol) was
treated according to the general procedure given above. The
crude product was purified by column chromatography (CH2Cl2/
MeOH 99.5:0.5!99:1) affording compound 17a as a red-orange
1
solid (25 mg, 64%): H NMR (300 MHz, [D6]DMSO): d=3.97 (s, 3H),
6.60 (brs, 2H), 6.93 (dd, J=6.3 Hz, J=2.4 Hz, 1H), 7.40–7.46 ppm
(m, 2H); 13C NMR (75 MHz, [D6]DMSO): d=55.81, 85.68, 105.61,
115.55, 120.19, 129.32, 140.08, 145.58, 157.16, 159.20, 173.68 ppm;
HRMS (ESI): m/z [MꢀH]ꢀ calcd for C11H9N3O2S2: 278.0063, found
278.0056.
5-(3-Amino-6-(trifluoromethyl)benzo[b]thiophen-2-yl)-1,3,4-oxa-
diazole-2(3H)-thione (20): Acyl hydrazide 19 (92 mg, 0.334 mmol)
was treated according to the general procedure given above. The
crude product was purified by column chromatography (CH2Cl2/
EtOAc 4:1) affording compound 20 as a yellow solid (62 mg, 58%):
1H NMR (300 MHz, [D6]DMSO): d=6.94 (brs, 2H), 7.77 (dd, J=
5-(3-Amino-4-(trifluoromethyl)benzo[b]thiophen-2-yl)-1,3,4-oxa-
diazole-2(3H)-thione (17b): Acyl hydrazide 16b (69 mg,
0.251 mmol) was treated according to the general procedure given
above. The crude product was purified by column chromatography
(CHCl3/MeOH 100:0!99:1) affording compound 17b as a yellow
solid (72 mg, 90%): 1H NMR (300 MHz, [D6]DMSO): d=6.10 (brs,
2H), 7.68 (t, J=7.8 Hz, 1H), 7.90 (d, J=7.5 Hz, 1H), 8.36 ppm (d, J=
8.4 Hz, J=1.2 Hz, 1H), 8.38 (d, J=8.4 Hz, 1H), 8.48 ppm (brs, 1H);
3
13C NMR (150 MHz, [D6]DMSO): d=90.75, 120.87, 121.10 (q, JC-F
=
3.3 Hz), 123.74, 124.26 (q, 1JC-F =272 Hz), 127.51 (q, 2JC-F =32 Hz),
134.13, 138.14, 144.12, 158.36, 175.37 ppm; 19F NMR (470 MHz,
[D6]DMSO): d=ꢀ60.38 ppm; HRMS (ESI): m/z [M+H]+ calcd for
C11H6F3N3OS2: 317.9977, found: 317.9977.
2
8.1 Hz, 1H); 13C NMR (150 MHz, [D6]DMSO): d=93.17, 122.97 (q, JC-
F =32 Hz), 123.81 (q, 3JC-F =6 Hz), 123.92 (q, 1JC-F =273 Hz), 125.64,
126.52, 128.84, 141.04, 142.51, 158.17, 175.42 ppm; 19F NMR
(150 MHz, [D6]DMSO): d=ꢀ54.85 ppm; HRMS (ESI): m/z [MꢀH]ꢀ
calcd for C11H6F3N3OS2: 315.9832, found 315.9839.
Benzo[b]thiophene-2-carbohydrazide (22a): This compound was
obtained from ethyl benzo[b]thiophene-2- carboxylate (21a), using
the procedure described for the synthesis of compound 4, yielding
the title compound as a brown solid (90%).
5-(3-Amino-5-methoxybenzo[b]thiophen-2-yl)-1,3,4-oxadiazole-
2(3H)-thione (17c): Acyl hydrazide 16c (80 mg, 0.316 mmol) was
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemMedChem 2014, 9, 2587 – 2601 2597