K. Hemming et al. / Tetrahedron 70 (2014) 7306e7317
7315
2.05 (3H, s, CH3), 6.16 (1H, s, pyrrole-H), 6.85 (1H, s, pyrrole-H), 7.05
4.21. Synthesis of 11-phenyl-[1,2,4-oxadiazolo]pyrrolo[1,2-b]
(1H, dd, J 2.6, 2.6, pyrrole-H), 7.23 (1H, dd, J 7.9, 7.9, ArH), 7.31 (1H, d,
J 7.6, ArH), 7.59 (1H, dd, J 7.6, 7.6, ArH), 7.79 (1H, d, J 7.9, ArH), 8.54
[1,2,5]benzothiadiazepine 5,5-dioxides 40aed
(1H, s, CHO), 9.40 (1H, br s, NH); 13C NMR
d
(100 MHz, CDCl3): 11.8
Typical procedure: A solution of benzohydroximoyl chloride or
ethyl chloroximidoacetate (1.00e2.00 mmol, 2.2 M equiv) in tet-
rahydrofuran (10e20 mL) was added dropwise over 10e12 h, with
stirring, to a mixture of the pyrrolo[1,2-b][1,2,5]benzothiadiazepine
5,5-dioxide (39a/b; 0.50e1.00 mmol, 1.0 M equiv) and triethyl-
amine (1.00e2.00 mmol, 2.2 M equiv) in anhydrous tetrahydrofu-
ran (10e20 mL) at ambient temperature. After stirring at room
temperature for a further 10e12 h, the volatiles were removed
under reduced pressure and the crude residue was purified by flash
column chromatography (PE/EtOAc; 1:2).
(CH3),116.5 (CH),117.4 (CH),120.5 (CH),123.2 (CH),124.6 (CH),125.4
(q), 126.0 (q), 128.8 (CH), 129.9 (q), 135.3 (CH), 158.9 (CHO); IR nmax
(cmꢂ1): 3299, 2953, 1705, 1677, 1580, 1517, 1467, 1433, 1406, 1361,
1291, 1261, 1174, 1096, 1038, 913, 829, 735, 692, 608; EIþ mass
spectrum (m/z, %): 264 ([M]þ, 50%), 184 (77%), 156 (45%), 120 (59%),
92 (81%), 81 (100%), 65 (95%), 53 (83%). C12H12N2O3S requires [M]þ
264; HRMS (CIþNH3): found [MþNH4]þ 282.0905, C12H16N3O3S
requires 282.0907.
1-(2-formamidobenzenesulfonyl)-3,4-dimethylpyrrole was ob-
tained as pale yellow oil (0.120 g, 83% yield) from 1-(2-
aminobenzenesulfonyl)-3,4-dimethylpyrrole (38b; 0.130 g,
4.21.1. 11-Phenyl-[1,2,4-oxadiazolo]-1-methylpyrrolo[1,2-b][1,2,5]
benzothiadiazepine 5,5-dioxide (40a). Compound 40a was ob-
tained as a pale yellow oil (0.085 g, 47% yield) from the pyrrolo
[1,2-b][1,2,5]benzothiadiazepine 5,5-dioxide (39a, 0.121 g,
0.52 mmol); Rf¼0.2 (PE/EtOAc; 2:3); 1H NMR
d (400 MHz, CDCl3):
1.97 (6H, s, 2ꢁCH3), 6.85 (2H, s, 2ꢁpyrrole-H), 7.23 (1H, dd, J 7.7,
7.7, ArH), 7.61 (1H, dd, J 7.7, 7.7, ArH), 7.77 (1H, d, J 8.0, ArH), 8.52
(1H, d, J 8.0, ArH), 8.56 (1H, s, CHO), 9.45 (1H, br s, NH); 13C NMR
0.49 mmol); Rf¼0.3 (PE/EtOAc; 1:2); 1H NMR
d (400 MHz, CDCl3):
d
(100 MHz, CDCl3): 10.1 (CH3), 117.5 (CH), 123.0 (CH), 124.2 (CH),
2.21 (3H, s, CH3), 6.14 (1H, d, J 3.2, pyrrole-H), 6.85 (1H, d, J 3.2,
pyrrole-H), 7.10 (1H, s, CHON), 7.20e7.30 (2H, m, 2ꢁArH),
7.30e7.50 (4H, m, 4ꢁArH), 7.57 (2H, d, J 7.7, 2ꢁArH), 7.94 (1H, dd, J
125.7 (q), 125.8 (CH), 126.1 (q), 128.8 (CH), 135.1 (CH), 158.8 (CHO);
IR nmax (cmꢂ1): 3290, 3020, 2921, 1706, 1674, 1579, 1514, 1403,
1358, 1290, 1216, 1160, 1071, 669; EIþ mass spectrum (m/z, %): 278
([M]þ, 60%), 250 (10%), 228 (60%), 184 (85%), 156 (20%), 120 (50%),
95 (100%), 65 (85%). C13H14N2O3S requires [Mþ] 278; HRMS
(CIþNH3): found [MþNH4]þ 296.1063, C13H18N3O3S requires
296.1063.
7.9, 1.4, ArH); 13C NMR
d (100 MHz, CDCl3): 11.8 (CH3), 91.9
(CHON), 115.5 (CH), 119.5 (q), 122.3 (CH), 124.4 (q), 125.5 (CH),
127.4 (CH), 127.7 (CH), 127.8 (q), 128.5 (CH), 128.8 (CH), 131.1 (CH),
132.8 (q), 134.4 (CH), 135.9 (q), 155.6 (q); IR nmax (cmꢂ1): 3145,
3087, 3066, 2927, 1660, 1585, 1477, 1444, 1408, 1358, 1258, 1179,
1156, 1089, 908, 836, 730, 694, 648; ESþ mass spectrum (m/z, %):
366 ([MþH]þ, 27%), 191 (21%), 132 (35%), 117 (26%), 85 (100%),
4.20.2. Step 2: ring closure. A solution of the 1-(2-
formamidobenzenesulfonyl)pyrrole (1.0 M equiv) and phospho-
C
C
19H16N3O3S requires 366; HRMS (ESIþ): found [MþH]þ 366.0905,
rus oxychloride (0.67e0.93 mL, 20e25
M
equiv) in di-
19H16N3O3S requires 366.0907.
chloroethane (2 mL) was heated at reflux temperature for 3 h.
Saturated sodium hydrogen carbonate solution (4 mL) and ethyl
acetate (4 mL) were added and the organic layer was separated
and dried over Na2SO4. Evaporation of the solvent gave a residue,
which was purified by flash silica column chromatography (PE/
EtOAc; 2:3).
4.21.2. 11-Phenyl-[1,2,4-oxadiazolo]-1,2-dimethylpyrrolo[1,2-b]
[1,2,5]benzothiadiazepine 5,5-dioxide (40b). Compound 40b was
obtained as pale yellow oil (0.201 g, 69% yield) in the same way
from 1,2-dimethylpyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-
dioxide (39b; 0.202 g, 0.78 mmol); Rf¼0.3 (PE/EtOAc; 1:2); 1H
The pyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-dioxides were
obtained as follows:
NMR d (400 MHz, CDCl3): 1.93 (3H, s, CH3), 2.10 (3H, s, CH3), 6.81
(1H, d, J 8.0, ArH), 7.07 (1H, s, CHON), 7.23 (1H, dd, J 7.2, 7.2, ArH),
7.30e7.40 (4H, m, 3ꢁArHþpyrrole-H), 7.45 (1H, dd, J 7.5, 7.5, ArH),
7.56 (2H, d, J 7.9, 2ꢁArH), 7.90 (1H, d, J 7.9, ArH); 13C NMR
1-Methylpyrrolo[1,2-b][1,2,5]benzothiadiazepine
5,5-dioxide
(39a) was obtained as pale yellow oil (0.067 g, 59% yield) from 1-
(2-formamidobenzenesulfonyl)-3-methylpyrrole
(0.121
g,
d (100 MHz, CDCl3): 9.5 (CH3), 10.0 (CH3), 92.0 (CH), 119.6 (q), 119.8
0.46 mmol); Rf¼0.2 (PE/EtOAc; 1:2); 1H NMR
d
(400 MHz, CDCl3):
(CH),124.2 (q),124.5 (q),125.3 (CH),127.3 (CH),127.5 (CH),128.2 (q),
128.4 (CH), 128.7 (q), 128.8 (CH), 131.1 (CH), 132.6 (q), 134.2 (CH),
135.9 (q); IR nmax (cmꢂ1): 3145, 3090, 3070, 1610, 1584, 1573, 1500,
1446, 1409, 1365, 1308, 1269, 1197, 1185, 1174, 1130, 1085, 905, 842,
774, 699; ESþ mass spectrum (m/z, %): 380 ([MþH]þ, 100%), 303
(10%), 277 (13%), 261 (35%), 249 (18%), 175 (10%), 141 (12%), 105
(18%), 89 (11%); HRMS (ESIþ): found [MþH]þ 380.1063,
2.37 (3H, s, CH3), 6.36 (1H, d, J 2.9, pyrrole-H), 7.44 (1H, dd, J 7.4, 7.4,
ArH), 7.51 (1H, d, J 2.9, pyrrole-H), 7.66e7.75 (2H, m, 2ꢁArH), 8.07
(1H, d, J 7.9, ArH), 8.66 (1H, s, N]CH); 13C NMR
d (100 MHz, CDCl3):
11.5 (CH3), 114.8 (CH), 123.0 (q), 123.1 (CH), 124.6 (q), 125.5 (CH),
126.5 (CH), 129.9 (CH), 133.0 (q), 134.6 (CH), 143.9 (q), 148.6 (N]
CH); IR nmax (cmꢂ1): 2927, 1603, 1580, 1466, 1365, 1259, 1187, 1149,
1069, 910, 829, 765; ESþ mass spectrum (m/z, %): 247 ([MþH]þ,
100%), 172 (54%), 130 (45%), 112 (33%), 88 (15%), 58 (15%),
C20H18N3O3S requires 380.1067.
C
C
12H11N2O2S requires 247; HRMS (ESþ): found [MþH]þ, 247.0532,
4.21.3. Ethyl [1,2,4-oxadiazolo]-1-methylpyrrolo[1,2-b][1,2,5]benzo-
thiadiazepine 5,5-dioxide 11-carboxylate (40c). Compound 40c was
obtained as a pale yellow oil (0.190 g, 66% yield) from 1-
methylpyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-dioxide (39a;
12H11N2O2S requires 247.0536.
1,2-Dimethylpyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-dioxide
(39b) was obtained as pale yellow oil (0.040 g, 43% yield) from 1-
(2-formamidobenzenesulfonyl)-3,4-dimethylpyrrole (c; 0.100 g,
0.203 g, 0.82 mmol); Rf¼0.2 (PE/EtOAc; 1:2); 1H NMR
d (400 MHz,
0.36 mmol); Rf¼0.2 (PE/EtOAc; 1:2); 1H NMR
d
(400 MHz, CDCl3):
CDCl3): 1.28 (3H, t, J 7.1, CO2CH2CH3), 2.12 (3H, s, CH3), 4.25 (2H, m,
CO2CH2CH3), 6.13 (1H, s, CHON), 7.11 (1H, s, pyrrole-H), 7.33 (1H, d, J
3.0, pyrrole-H), 7.54 (1H, dd, J 7.7, 7.7, ArH), 7.63 (1H, d, J 7.7, ArH),
7.70 (1H, dd, J 7.7, 7.7, ArH), 7.95 (1H, d, J 7.7, ArH); 13C NMR
2.06 (3H, s, CH3), 2.26 (3H, s, CH3), 7.33 (1H, s, pyrrole-H), 7.42 (1H,
ddd, J 8.0, 8.0, 1.0, ArH), 7.60e7.73 (2H, m, 2ꢁArH), 8.04 (1H, dd, J
8.0, 1.2, ArH), 8.62 (1H, s, N]CH); 13C NMR
d (100 MHz, CDCl3): 9.6
(CH3), 9.9 (CH3), 120.8 (CH), 123.6 (q), 124.9 (q), 125.3 (CH), 126.2
(CH), 129.9 (CH), 130.1 (q), 132.5 (q), 134.4 (CH), 144.1 (q), 148.6 (N]
CH); IR nmax (cmꢂ1): 2924, 1603, 1582, 1458, 1365, 1294, 1181, 1137,
1107, 910, 832, 767; ESþ mass spectrum (m/z, %): 261 ([MþH]þ,
100%), 86 (4%), 58 (25%); HRMS (ESIþ): found [MþH]þ 261.0691,
d (100 MHz, CDCl3): 11.2 (CH3), 13.8 (CH3), 62.7 (CH2), 91.3 (CH),
114.0 (CH), 121.1 (q), 123.9 (CH), 127.1 (CH), 129.0 (CH), 130.2 (q),
133.6 (CH), 134.5 (CH), 137.8 (q), 147.8 (q), 156.6 (q); IR nmax (cmꢂ1):
3159, 3100, 3020, 2926, 1736, 1574, 1485, 1444, 1416, 1362, 1287,
1259, 1214, 1193, 1153, 1094, 1020, 913, 763; ESþ mass spectrum (m/
z, %): 362 ([MþH]þ, 100%), 316 (10%), 282 (16%), 247 (15%), 89 (24%),
C
13H13N2O2S requires 261.0692.