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D. Phillips et al. / Bioorg. Med. Chem. 10 (2002) 1229–1248
J=7.5 Hz, 1H), 6.02 (s, 1H), 4.81 (m, 1H), 2.50
(obscured by NMR solvent, 2H), 1.55 (m, 2H), 1.50 (d,
J=6.3 Hz, 3H), 0.93 (d, J=7.3 Hz, 3H); 13C NMR
(125 MHz, DMSO-d6) d 141.6, 132.7, 128.2, 122.0,
121.8, 116.5, 62.4, 37.4, 21.4, 20.66, 14.1. FTIR (KBr)
3386, 3212, 2957, 2939, 2873, 1654, 1599, 1499, 1449,
(300 MHz, DMSO-d6) d 7.45 (d, J=11.8 Hz, 1H), 7.26
(d, J=8.1 Hz, 1H), 6.63 (d, J=8.1 Hz, 1H), 5.91 (s,
1H), 4.79 (m, 1H), 2.22 (s, 3H), 2.04 (s, 3H), 1.49 (d,
J=6.2 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) d
142.2, 140.9, 122.4, 121.1, 120.4, 119.2, 62.6, 21.1, 20.1,
13.6. FTIR (KBr) 3407, 3198, 2990, 1596, 1507, 1474,
1447, 1384, 1301, 1284 cm À1. HRMS (CI) calcd for
C10H14N2O2S [M+] 226.0776, found 226.0780.
1384, 1314, 1290 cmÀ1
. HRMS (CI) calcd for
C11H16N2O2S [M+] 240.0932, found 240.0931.
7-Chloro-3,5-dimethyl-3,4-dihydro-2H-benzo[1,2,4]thia-
diazine 1,1-dioxide (16g). This was prepared from 4-
chloro-2-methylaniline by the general procedures A and
C to give a white powder (33%, three steps); mp 256–
258 ꢀC. 1H NMR (500 MHz, DMSO-d6) d 7.71 (d,
J=11.8 Hz, 1H), 7.36 (s, 1H), 7.30 (d, J=1.5 Hz, 1H),
6.21 (s, 1H), 4.83 (m, 1H), 2.16 (s, 3H), 1.50 (d, J=6.0
Hz, 3H); 13C NMR (75 MHz, DMSO-d6) d 141.3, 133.3,
127.4, 122.4, 120.8, 120.1, 62.6, 20.5, 18.0. FTIR (KBr)
3418, 3222, 2988, 2940, 1601, 1497, 1466, 1449, 1420,
1383, 1313 cm À1. HRMS for C9H11ClN2O2S [M+]
calcd 246.0230, found 246.0230.
6-Chloro-3,5-dimethyl-3,4-dihydro-2H-benzo[1,2,4]thia-
diazine 1,1-dioxide (16l). This was prepared from 3-
chloro-2-methylaniline by the general procedures A and
C to give a tan powder (72%, three steps); mp 184–
187 ꢀC. 1H NMR (300 MHz, DMSO-d6) d 7.67 (d,
J=11.8 Hz, 1H), 7.39 (d, J=8.6 Hz, 1H), 6.85 (d,
J=8.5 Hz, 1H), 6.34 (s, 1H), 4.85 (m, 1H), 2.22 (s, 3H),
1.51 (d, J=6.2 Hz, 3H); 13C (75 MHz, DMSO-d6) d
138.0, 123.6, 122.5, 121.4, 118.2, 63.4, 21.2, 15.4. FTIR
(KBr) 3400, 3220, 2992, 1578, 1499, 1445, 1384, 1319,
1288 cmÀ1. HRMS (CI) calcd for C9H11ClN2O2S [M+]
246.0230, found 246.0230.
7-Fluoro-3,5-dimethyl-3,4-dihydro-2H-benzo[1,2,4]thia-
diazine 1,1-dioxide (16 h). This was prepared from 4-
fluoro-2-methyl aniline by the general procedures A and
C to give a white solid (60%, three steps); mp 211–
214 ꢀC. 1H (500 MHz, DMSO-d6) d 7.67 (d, J=11.9 Hz,
1H), 7.21 (s, 1H), 7.18 (s, 1H), 5.97 (s, 1H), 4.80 (m,
1H), 2.17 (s, 3H), 1.49 (d, J=6.1 Hz, 3H); 13C NMR
(125 MHz, DMSO-d6) d 154.0 (d, J=236.3 Hz), 139.8,
128.3 (d, J=8.0 Hz), 122.1, 122.0 (d, J=23.9 Hz), 107.9
(d, J=23.6 Hz), 63.3, 21.2, 18.7. FTIR (KBr) 3394, 3223,
2924, 1499, 1384, 1316, 1238 cm À1. HRMS (CI) calcd
for C9H11FN2O2S [M+] 230.0525, found 230.0524.
8-Chloro-3,5-dimethyl-3,4-dihydro-2H-benzo[1,2,4]thia-
diazine 1,1-dioxide (16m). This was prepared from 5-
chloro-2-methyl aniline by the general procedures A and
C to give a tan powder (42%, three steps); mp 219–
220 ꢀC. 1H NMR (500 MHz, DMSO-d6) d 7.85 (d,
J=8.8 Hz, 1H), 7.15 (d, J=7.9 Hz, 1H), 6.74 (d, J=7.9
Hz, 1H), 6.20 (s, 1H), 4.77 (m, 1H), 2.12 (s, 3H), 1.49 (d,
J=6.2 Hz, 3H); 13C NMR (125 MHz, DMSO-d6) d
144.2, 133.0, 127.5, 123.3, 120.0, 117.9, 61.1, 19.8, 17.7.
FTIR (KBr) 3397, 3210, 2923, 1594, 1560, 1499, 1459,
1380, 1320, 1300, 1239 cmÀ1. HRMS (CI) calcd for
C9H11ClN2O2S [M+] 246.0230, found: 246.0233.
3,5,7-Trimethyl-3,4-dihydro-2H-benzo[1,2,4]thiadiazine
1,1-dioxide (16i). This was prepared from 2,4-dimethy-
laniline by the general procedures A and C to give a tan
5-Fluoro-3-methyl-3,4-dihydro-2H-benzo[1,2,4]thiadia-
zine 1,1-dioxide (16n). This was prepared from 2-fluor-
oaniline by the general procedꢀures A and C to give a
ꢀ
1
1
powder (16%, three steps); mp 225–230 C. H NMR
(500MHz, DMSO-d6) d 7.48 (d, J=11.9 Hz, 1H), 7.16 (s,
1H), 7.04 (s, 1H), 5.83 (s, 1H), 4.79 (m, 1H), 2.18 (s, 3H),
2.12 (s, 3H), 1.48 (d, J=6.1 Hz, 3H); 13C NMR
(125MHz, DMSO-d6) d 140.1, 134.9, 125.6, 124.6, 122.0,
121.3, 62.6, 20.7, 20.2, 18.1. FTIR (KBr) 3399, 3191,
1618, 1501, 1448, 1384, 1314, 1291 cm À1. HRMS (CI)
calcd for C10H14N2O2S [M+] 226.0776, found 226.0773.
yellowish powder; mp 208–210 C. H NMR (500 MHz,
DMSO-d6) d 7.73 (d, J=11.7 Hz, 1H), 7.34 (d, J=7.9
Hz, 1H), 7.29 (dd, J=11.4, 8.2 Hz, 1H), 6.99 (s, 1H),
6.73 (dd, J=7.8, 4.7 Hz, 1H), 4.86 (m, 1H), 1.48 (d,
J=6.1 Hz, 3H). FTIR (KBr) 3367, 3215, 1618, 1500,
1315, 1248 cmÀ1. HRMS (CI) calcd for C8H9FN2O2S
[M+] 216.0368, found 216.0368.
7-chloro-5-fluoro-3-methyl-3,4-dihydro-2H-1,2,4-benzo-
thiadiazine-1,1-dioxide (16o). This was prepared from
16n by the general procedure B to give a brown solid;
7-Chloro-3,5,6-trimethyl-3,4-dihydro-2H-benzo[1,2,4]-
thiadiazine 1,1-dioxide (16j). This was prepared from
16k by the general procedure B to give an off-white
powder in 100% yield; mp 251–253 ꢀC. 1H NMR
(300 MHz, DMSO-d6) d 7.67 (d, J=11.7 Hz, 1H), 7.38
(s, 1H), 6.10 (s, 1H), 4.81 (m, 1H), 2.30 (s, 3H), 2.13 (s,
3H), 1.50 (d, J=6.1 Hz, 3H); 13C NMR (75 MHz,
DMSO-d6) d 141.7, 139.0, 125.9, 122.6, 121.6, 121.5, 63.2,
21.2, 18.2, 15.4. FTIR (KBr) 3415, 3194, 2923, 1591,
1499, 1458, 1388, 1302, 1285 cmÀ1. HRMS (CI) calcd
for C10H13ClN2O2S [M+] 260.0386, found 260.0375.
mp 194–196 ꢀC. H NMR (500 MHz, DMSO-d6) d 7.90
1
(d, J=11.6 Hz, 1H), 7.53 (dd, J=11.3, 1.8 Hz, 1H), 7.41
(s, 1H), 7.22 (s, 1H), 4.87 (m, 1H), 1.48 (d, J=6.1 Hz,
3H). FTIR (KBr) 3365, 3240, 2924, 1499, 1337, 1252
cmÀ1. HRMS (CI) calcd for C8H8ClFN2O2S [M+]
249.9978, found 249.9972.
5-chloro-3,7-dimethyl-3,4-dihyrdo-2H-1,2,4-benzothiadia-
zine-1,1-dioxide (16p). This was prepared from 2-chloro-
4-methylaniline by the general procedures A and C to
give an off-white powder (54%, three steps); mp 239–
242 ꢀC. 1H NMR (500 MHz, DMSO-d6) d 7.76 (d,
J=11.7 Hz, 1H), 7.37 (s, 1H), 7.34 (s, 1H), 6.31 (s, 1H),
4.86 (m, 1H), 2.22 (s, 3H), 1.50 (d, J=6.1 Hz, 3H); 13C
3,5,6-Trimethyl-3,4-dihydro-2H-benzo[1,2,4]thiadiazine
1,1-dioxide (16k). This was prepared from 2,3-dimethyl-
aniline by the general procedures A and C to give a tan
powder (46%, three steps); mp 251–253 ꢀC. H NMR
1