S. Ahmad et al.
EuropeanJournalofPharmaceuticalSciences131(2019)9–22
Yield: 87%; m.p 252–254 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
ArH); 13C NMR (DMSO‑d6, 125 MHZ)δ (ppm): 31.5, 37.1, 58.1, 113.2,
116.3, 118.3, 123.8, 124.9, 129.1(3C), 130.2(2C), 132.6, 133.0, 139.3,
142.1, 146.9, 159.1; LC-MS (m/z): calcd: 398 [M−H]−; found: 398.42
(ppm):5.09 (s, 2H, CH2), 5.54 (s, 1H, CH), 7.01 (d, 2H, J = 6.6 Hz,
ArH), 7.21 (s, 2H,NH2), 7.22 (s, 1H, ArH), 7.38 (t, 1H, J = 7.6 Hz, ArH),
7.50 (d, 1H, J = 8.4 Hz, ArH), 7.56–7.64 (m, 5H, ArH), 7.79 (t, 1H,
J = 7.6 Hz, ArH), 7.96 (t, 2H, J = 9.8 Hz, ArH); 13C NMR (DMSO‑d6,
125 MHZ)δ (ppm): 32.5, 48.9, 56.5, 113.4, 117.2, 118.9, 119.8, 124.3,
124.9, 125.1, 127.5 (2C), 128.1, 128.9(2C), 129.6, 132.1, 132.9, 134.5,
135.9, 137.0, 137.8, 147.1, 149.0, 159.9; LC-MS (m/z): calcd: 485
[M−H]−, 487 [M+H]+, 509 [M+Na]+, 525 [M+K]+; found: 485.33
[M−H]−
.
2-Amino-4-(4-chlorophenyl)-6-methyl-4,6-dihydrobenzo[c]pyrano
[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxide (7c)
Yield: 94%; m.p222–224 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):3.32 (s, 3H, CH3), 4.75 (s, 1H, CH), 7.34 (s, 2H, NH2), 7.41–7.44
(m, 5H, ArH), 7.47 (d, 1H, J = 8.2 Hz, ArH), 7.70 (t, 1H, J = 7.9 Hz,
ArH), 7.97 (dd, 1H, J1 = 8, J2 = 1.4 Hz, ArH); 13C NMR (DMSO‑d6, 125
MHZ)δ (ppm): 31.5, 37.2, 58.1, 113.2, 116.3, 118.3, 119.2, 123.8,
124.9, 129.1(2C), 130.2(2C), 132.6, 133.0, 139.3, 142.1, 146.9, 159.2;
[M−H]−, 487.25[M+H]+, 509.25 [M+Na]+, 525.17[M+K]+
2-Amino-6-benzyl-4-(3-nitrophenyl)-4,6-dihydrobenzo[c]pyrano
[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxide (6p)
.
Yield: 90%; m.p230–232 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):5.13 (s, 2H, CH2), 5.11 (s, 1H, CH), 7.07 (d, 2H, J = 6.8 Hz,
ArH), 7.20 (d, 3H, J = 6.2 Hz,ArH), 7.38 (t, 1H, J = 7.6 Hz, ArH),
7.51(s, 1H, ArH), 7.54 (s, 2H, NH2), 7.60 (t, 1H, J = 7.5 Hz, ArH), 7.72
(t, 1H, J = 7.9 Hz, ArH), 7.87 (d, 1H, J = 7.7 Hz, ArH), 7.97 (d, 1H,
J = 7.2 Hz, ArH),8.20 (d, 2H, J = 7.6 Hz, ArH); 13C NMR (DMSO‑d6,
125 MHZ)δ (ppm): 37.2, 48.9, 57.5, 113.7, 117.3, 119.1, 119.8, 122.9,
123.2, 124.3, 125.1, 127.6(2C), 128.1, 128.9(2C), 130.8, 132.9, 135.4,
135.9, 137.8, 145.4, 147.2, 148.3, 159.4; LC-MS (m/z): calcd: 485
LC-MS (m/z): calcd: 398 [M−H]−; found: 398.25 [M−H]−
.
2-Amino-4-(2,4-dichlorophenyl)-6-methyl-4,6-dihydrobenzo[c]
pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxide (7d)
Yield: 81%; m.p236–238 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):3.32 (s, 3H, CH3), 5.18(s, 1H, CH), 7.42–7.44 (m, 1H, ArH), 7.46
(s, 1H, ArH),7.48 (s, 2H, NH2), 7.47 (d, 2H, J = 6 Hz, ArH), 7.49 (s, 1H,
ArH), 7.62 (s, 1H, ArH), 7.71 (t, 1H, J = 7.8 Hz, ArH), 7.97 (d, 1H,
J = 7.5 Hz, ArH); 13C NMR (DMSO‑d6, 125 MHZ)δ (ppm): 31.6, 116.2,
118.4(2C), 118.9, 123.9 (2C), 124.9(2C), 128.4, 129.6, 133.1(3C),
[M−H]−, 509 [M+Na]+, 525 [M+K]+; found: 485.25 [M−H]−
,
133.5, 133.8, 139.3, 147.4, 159.4; LC-MS (m/z): calcd: 432 [M−H]−
434 [M+H]+, 456 [M+Na]+, 472 [M+K]+; found: 432.17 [M−H]−
,
,
509.17 [M+Na]+, 525.17 [M+K]+
.
2-Amino-6-benzyl-4-(m-tolyl)-4,6-dihydrobenzo[c]pyrano[2,3-e]
[1,2]thiazine-3‑carbonitrile 5,5-dioxide (6q)
434.25 [M+H]+, 456.17 [M+Na]+, 472.08 [M+K]+
.
2-Amino-4-(2-bromophenyl)-6-methyl-4,6-dihydrobenzo[c]pyrano
[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxide (7e)
Yield: 96%; m.p 221–223 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):2.31(s, 3H, CH3), 4.70 (s, 1H, CH), 5.14 (d, 2H, J = 4 Hz, CH2),
7.11 (t, 5H, J = 6.7 Hz, ArH), 7.21 (s, 2H, NH2), 7.23(d, 1H, J = 7 Hz,
ArH), 7.27(t, 1H, J = 7.9 Hz, ArH), 7.36(t, 3H, J = 7.4 Hz, ArH),
7.50(d, 1H, J = 8.1 Hz, ArH), 7.58(t, 1H, J = 7.9 Hz, ArH), 7.94(dd,
1H, J1 = 8 Hz, J2 = 1.4 Hz, ArH); 13C NMR (DMSO‑d6, 125 MHZ)δ
(ppm): 21.6, 37.9, 48.9, 58.6, 114.9, 117.5, 119.4, 119.8, 124.2, 124.9,
125.4, 127.7(2C), 128.1(2C), 128.6(2C), 128.8, 128.9, 132.6, 136.0,
Yield: 88%; m.p235–237 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):3.31 (s, 3H, CH3), 5.19 (s, 1H, CH), 7.22 (t, 1H, J = 6.9 Hz, ArH),
7.37 (s, 2H, NH2), 7.43 (t, 3H, J = 7.4 Hz, ArH), 7.48 (d, 1H,
J = 8.3 Hz, ArH), 7.61 (d, 1H, J = 7.9 Hz, ArH), 7.71 (t, 1H, J = 7.7 Hz,
ArH), 7.98 (d, 1H, J = 7.8 Hz, ArH); 13C NMR (DMSO‑d6, 125 MHZ)δ
(ppm): 31.6(2C), 116.3, 118.4(2C), 123.1, 123.9(2C), 124.9(2C),
128.8, 130.0(2C), 133.1(2C), 139.3(2C), 147.3, 159.3; LC-MS (m/z):
calcd: 442, 444 [M−H]−, 466, 468 [M+Na]+, 484 [M+K]+; found:
442.08, 444.25 [M−H]−, 466.08, 468.08 [M+Na]+, 484.08 [M
137.8, 138.2, 143.0, 146.7, 159.2; LC-MS (m/z): calcd: 454 [M−H]−
456 [M+H]+, 478 [M+Na]+, 494 [M+K]+; found: 454.33 [M−H]−
,
,
456.25 [M+H]+, 478.33 [M+Na]+, 494.25 [M+K]+
.
+K]+
.
2-Amino-6-benzyl-4-(3-ethoxy-4-hydroxyphenyl)-4,6-dihy-
2-Amino-4-(4-bromophenyl)-6-methyl-4,6-dihydrobenzo[c]pyrano
[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxide (7f)
drobenzo[c]pyrano[2,3-e][1,2]thiazine-3‑carbonitrile
(6r)
5,5-dioxide
Yield: 91%; m.p225–227 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):3.32 (s, 3H, CH3), 4.74 (s, 1H, CH), 7.28(d, 2H, J = 8.4 Hz, ArH),
7.41 (d, 1H, J = 7.6 Hz, ArH),7.43 (s, 2H, NH2), 7.48 (d, 1H,
J = 8.3 Hz, ArH), 7.55 (d, 2H, J = 8.4 Hz, ArH), 7.70 (t, 1H, J = 8.2 Hz,
ArH), 7.97 (dd, 1H, J1 = 8, J2 = 1.4 Hz, ArH); 13C NMR (DMSO‑d6, 125
MHZ)δ (ppm): 31.5, 37.2, 57.9, 113.5, 116.3, 118.3, 119.2, 121.2,
123.8, 124.9, 130.5(2C), 131.9(2C), 133.1, 139.3, 142.5, 146.9, 159.1;
LC-MS (m/z): calcd: 468 [M+Na]+, 482, 484 [M+K]+; found: 468.08
Yield: 86%; m.p173–175 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):1.31 (t, 3H, J = 7 Hz, CH3), 3.92–4.02 (q, 2H, CH2), 4.62 (s, 1H,
CH), 5.14 (s, 2H, CH2Ph), 6.69 (dd, 1H, J1 = 8.1 Hz, J2 = 1.4 Hz, ArH),
6.79 (d, 1H, J = 8.1 Hz, ArH), 6.85 (s, 1H, ArH), 7.09 (d, 2H,
J = 7.4 Hz, ArH), 7.21(s, 3H, J = 7.4 Hz, ArH), 7.29 (s, 2H, NH2), 7.35
(t, 1H, J = 7.6 Hz, ArH), 7.49 (d, 1H, J = 8.3 Hz, ArH), 7.56 (t, 1H,
J = 7.8 Hz), 7.91 (d, 1H, J = 7.9 Hz, ArH), 8.96 (s, 1H, OH); 13C NMR
(DMSO‑d6, 125 MHZ)δ (ppm): 15.1, 37.6, 49.1, 58.9, 64.4, 114.1,
115.4, 116.1, 117.7, 119.8, 120.8, 124.2, 124.9, 127.7(3C), 128.1,
128.9 (3C), 132.5, 133.8, 136.1, 137.7, 146.2, 146.8, 159.2; LC-MS (m/
z): calcd: 500 [M−H]−, 524 [M+Na]+, 540 [M+K]+; found: 500.17
[M+Na]+, 482.08, 484.08 [M+K]+
.
2-Amino-4-(2-methoxyphenyl)-6-methyl-4,6-dihydrobenzo[c]
pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxide (7g)
Yield: 72%; m.p190–192 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):3.31 (s, 3H, CH3), 3.74 (s, 3H, OCH3), 4.92 (s, 1H, CH), 6.91 (t,
1H, J = 7.3 Hz, ArH), 7.02 (d, 1H, J = 8 Hz, ArH), 7.14 (dd, 1H,
J1 = 7.6, J2 = 1.5 Hz, ArH), 7.24 (s, 2H, NH2), 7.26 (d, 1H, J = 8.5 Hz,
ArH), 7.43 (quintet, 1H, J = 8.1 Hz, ArH), 7.68 (t, 2H, J = 7.8 Hz, ArH),
7.98 (dd, 1H, J1 = 7.9, J2 = 1.2 Hz, ArH); 13C NMR (DMSO‑d6, 125
MHZ)δ (ppm): 31.3, 32.7, 56.4, 57.4, 112.4, 112.9, 116.4, 118.2, 119.5,
121.1, 123.7, 124.6, 129.4, 129.6, 130.5, 132.7, 139.2, 147.2, 157.5,
159.9; LC-MS (m/z): calcd: 394 [M−H]−, 418 [M+Na]+, 434 [M
[M−H]−, 524.17 [M+Na]+, 540.17 [M+K]+
.
2-Amino-6-methyl-4-phenyl-4,6-dihydrobenzo[c]pyrano[2,3-e]
[1,2]thiazine-3‑carbonitrile 5,5-dioxide (7a)
Yield: 86%; m.p228–230 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ (ppm):
3.32 (s, 3H,CH3), 4.68 (s, 1H, CH), 7.28(d, 3H, J = 8.0 Hz, ArH), 7.35
(d, 2H, J = 7.2 Hz, ArH), 7.38 (s, 2H, NH2), 7.42 (t, 1H, J = 7.6 Hz,
ArH), 7.48 (d, 1H, J = 8.2 Hz, ArH), 7.70(t, 1H, J = 7.9 Hz, ArH), 7.98
(dd, 1H, J1 = 7.9, J2 = 1.3 Hz, ArH); LC-MS (m/z): calcd: 364
[M−H]−, 366 [M+H]+, 388 [M+Na]+, 404 [M+K]+; found: 364.25
+K]+; found: 394.25 [M−H]−, 418.25 [M+Na]+, 434.17 [M+K]+
2-Amino-4-(4-methoxyphenyl)-6-methyl-4,6-dihydrobenzo[c]
pyrano[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxide (7h)
.
[M−H]−, 366.17 [M+H]+, 388.17 [M+Na]+, 404.08 [M+K]+
.
2-Amino-4-(2-chlorophenyl)-6-methyl-4,6-dihydrobenzo[c]pyrano
[2,3-e][1,2]thiazine-3‑carbonitrile 5,5-dioxide (7b)
Yield: 73%; m.p200–202 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):3.32 (s, 3H, CH3), 3.75 (s, 3H, OCH3),4.62 (s, 1H, CH), 6.90 (d,
2H, J = 8.7 Hz, ArH), 7.21 (d, 2H, J = 8.7 Hz, ArH), 7.33 (s, 2H, NH2),
7.41 (t, 1H, J = 7.5 Hz, ArH), 7.46 (d, 1H, J = 8.2 Hz, ArH), 7.69 (t, 1H,
J = 7.8 Hz, ArH), 7.96 (dd, 1H, J = 7.9, J2 = 1.2 Hz, ArH); 13C NMR
Yield: 95%; m.p218–220 °C; 1H NMR (DMSO‑d6, 500 MHZ) δ
(ppm):3.32 (s, 3H, CH3), 4.75 (s, 1H, CH), 7.33 (s, 1H, ArH), 7.34 (s,
1H, ArH), 7.41 (s, 2H, NH2), 7.42 (s, 3H, ArH), 7.48 (d, 1H, J = 8.3 Hz,
ArH), 7.70(t, 1H, J = 7.9 Hz, ArH), 7.97 (dd, 1H, J1 = 7.9, J2 = 1.4 Hz,
19