3-(4-bromobenzoyl)-4-hydroxy-2-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl}-2H-1,2-benzothiazine
1,1-dioxide (6a) Yellow powder, 40% yield, mp 124-127 ºC; FT-IR (cm-1): 1610 (C=O), 1340, 1180 (SO2).
1H NMR (300 MHz, CDCl3) δ (ppm): 1.44 (brs, 2H, CH2CH2CH2), 2.51 (brs, 4H, CH2CH2CH2), 3.10 (brs,
13
8H, piperazine), 3.85 (s, 3H, OCH3), 6.84-8.18 (m, 12H, ArH). C NMR (300 MHz, DMSO-d6) δ (ppm):
152.14, 132.93, 131.72, 131.30, 128.12, 123.65, 121.08, 118.41, 111.25, 55.38, 52.88, 49.38, 23.40. HRMS
(ESI) calcd. for C29H30BrN3O5S [M+H]+ 611.1089; found 611.1139. Anal. calcd. for C29H30BrN3O5S: C,
56.86; H, 4.94; N, 6.86; Found: C, 56.56; H, 4.81; N, 6.63.
3-(4-chlorobenzoyl)-4-hydroxy-2-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl}-2H-1,2-benzothiazine
1,1-dioxide (6b) Yellow powder, 35% yield, mp 182-185 ºC; FT-IR (cm-1): 1600 (C=O), 1340, 1175 (SO2).
1H NMR (300 MHz, CDCl3) δ (ppm): 1.55 (brs, 2H, CH2CH2CH2), 2.36 (brs, 2H, CH2CH2CH2-piperazine),
2.68 (brs, 2H, CH2CH2CH2-piperazine), 3.16 (m, 8H, piperazine), 3.86 (s, 3H, OCH3), 6.85-8.21 (m, 12H,
13
ArH). C NMR (300 MHz, DMSO-d6) δ (ppm): 152.11, 133.01, 131.12, 130.79, 128.75, 128.38, 128.15,
123.70, 121.09, 118.46, 117.39, 111.27, 55.39, 52.73, 48.95, 23.08. HRMS (ESI) calcd. for C29H30ClN3O5S
[M+H]+ 567.1594; found 567.1664. Anal. calcd. for C29H30ClN3O5S: C, 61.31; H, 5.32; N, 7.40; Found: C,
61.16; H, 5.33; N, 7.17.
4-hydroxy-2-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl}-3-(4-methylbenzoyl)-2H-1,2-benzothiazine
1,1-dioxide (6c) Yellow powder, 38% yield, mp 163-166 ºC; FT-IR (cm-1): 1600 (C=O), 1340, 1175 (SO2).
1H NMR (300 MHz, CDCl3) δ (ppm): 1.39 (brs, 2H, CH2CH2CH2), 2.07 (brs, 2H, CH2CH2CH2-piperazine),
2.38 (brs, 4H, CH2CH2CH2 and 2Hpiperazine), 2.46 (s, 3H, CH3), 3.01 (brs, 6H, piperazine), 3.85 (s, 3H, OCH3),
6.84-8.22 (m, 12H, ArH). 13C NMR (300 MHz, DMSO-d6) δ (ppm): 191.27, 152.18, 140.87, 138.41, 133.44,
132.74, 129.53, 129.22, 127.85, 123.33, 123.14, 121.02, 118.24, 116.92, 111.22, 55.33, 55.11, 52.89, 51.78,
49.96, 23.37, 21.76. HRMS (ESI) calcd. for C30H33N3O5S [M+H]+ 547.2141; found 547.2208. Anal. calcd.
for C30H33N3O5S: C, 65.79; H, 6.07; N, 7.67; Found: C, 65.44; H, 6.15; N, 7.60.
4-hydroxy-3-(4-methoxybenzoyl)-2-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl}-2H-1,2-benzothiazine
1,1-dioxide (6d) Yellow powder, 47% yield, mp 147-149 ºC; FT-IR (cm-1): 1610 (C=O), 1360, 1180 (SO2).
1H NMR (300 MHz, CDCl3) δ (ppm): 1.38 (brs, 2H, CH2CH2CH2), 2.08 (brs, 2H, CH2CH2CH2-piperazine),
2.39 (brs, 4H, CH2CH2CH2 and 2Hpiperazine), 2.99 (brs, 6H, piperazine), 3.83 (s, 3H, OCH3 from
phenylpiperazine), 3.90 (s, 3H, OCH3 from benzoyl), 6.83-8.21 (m, 12H, ArH). 13C NMR (300 MHz, DMSO-
d6) δ (ppm): 190.29, 163.46, 152.18, 140.89, 138.29, 133.35, 132.74, 131.92, 127.79, 123.27, 123.14, 121.01,
118.23, 116.57, 113.90, 111.21, 55.51, 55.32, 55.09, 52.89, 51.62, 49.99, 23.23. HRMS (ESI) calcd. for
C30H33N3O6S [M+H]+ 563.2090; found 563.2149. Anal. calcd. for C30H33N3O6S: C, 63.92; H, 5.90; N, 7.45;
Found: C, 64.25; H, 6.25; N, 7.07.
General procedure for the preparation of series B compounds (7a – 7h)
The corresponding 1,2-benzothiazine 3a - 3e (5 mmol) was dissolved in 20 ml of anhydrous ethanol with the
addition of 5 ml of EtONa (2.3%). Then 5 mmol of corresponding arylpiperazine 5a - 5c were added and