10
Bioorganic Chemistry
Compound (3g) was synthesized from 4-chlorophenyl isocyanate (0.25 g, 1.627 mmol) and 1-((2-fluorophenyl)(4-
fluorophenyl)methyl)piperazine (0.469 g, 1.627 mmol) according to the general procedure. White solid. Yield = 70% (0.50 g). 1H NMR
(CDCl3, 500 MHz) δ 7.57 (t, J = 7.0 Hz, 1H), 7.40 (dd, J = 8.0, 6.0 Hz, 2H), 7.27-7.25 (m, 2H), 7.21-7.18 (m, 3H), 7.13 (t, J = 7.5 Hz,
1H), 6.99 (t, J = 8.5 Hz, 3H), 6.50 (s, 1H), 4.70 (s, 1H), 3.47 (t, J = 4.5 Hz, 4H), 2.46-2.39 (m, 4H). 13C NMR (CDCl3, 125 MHz) δ 161.1
(d, 1JC,F= 244.4 Hz), 160.6 (d, 1JC,F = 245.6 Hz), 154.7, 137.5, 136.8, 129.5 (d, 3JC,F = 7.1 Hz), 128.8, 128.6 (d, 3JC,F = 8.4 Hz), 128.4,
128.0, 124.4, 121.2, 115.8, 115.6, 115.4, 65.9, 51.2, 44.1. IR (KBr): ῡ = 3264.76, 2818.08, 2951.4, 1640.27, 1508.64, 1280.07, 825.60.
LC-MS for C24H22ClF2N3O: m/z = 442 [M+H]+.
4.2.1.8. Synthesis of N-(4-chlorophenyl)-4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazine-1-carboxamide (3h)
Compound (3h) was synthesized from 4-chloro phenyl isocyanate (0.25 g, 1.627 mmol) and 11-Piperazin-1-yl-dibenzo [b,f][1,4]
thiazepine (0.48 g, 1.627 mmol) according to the general procedure. White solid. Yield = 72% (0.526 g). 1H NMR (CDCl3, 500 MHz) δ
7.54 (d, J = 7.5 Hz, 1H), 7.41 (dd, J = 7.3, 1.0 Hz, 1H), 7.39-7.35 (m, 1H), 7.34-7.30 (m, 4H), 7.24-7.18 (m, 3H), 7.11 (dd, J = 8.0, 1.0
Hz, 1H), 6.93 (td, J = 7.5, 1.5 Hz, 1H), 6.65 (s, 1H), 3.73-3.48 (m, 8H). 13C NMR (CDCl3, 125 MHz) δ 160.7, 154.9, 140.0, 137.5, 133.6,
132.3, 132.2, 131.2, 129.2, 129.0, 128.9,128.8, 128.5, 128.2, 125.3, 123.5, 121.3, 43.6. IR (KBr): ῡ = 3356, 2840.53, 2891.01, 1626.31,
1518.95, 1239.22, 803.49. LC-MS for C24H21ClN4OS: m/z = 449 [M+H]+.
4.2.1.9. Synthesis of 4-benzhydryl-N-(4-fluorophenyl) piperazine-1-carboxamide (3i)
Compound (3i) was synthesized from 4-fluorophenyl isocyanate (0.25 g, 1.823 mmol) and 1-benzhydrylpiperazine (0.46 g, 1.823
mmol) according to the general procedure. White solid. Yield = 77% (0.546 g). 1H NMR (CDCl3, 500 MHz) δ 7.42 (d, J = 7.0 Hz, 4H),
7.31-7.28 (m, 6H), 7.22-7.17 (m, 2H), 6.98-6.93 (m, 2H), 6.31 (s, 1H), 4.26 (s, 1H), 3.47 (s, 4H), 2.43 (s, 4H). 13C NMR (CDCl3, 125
MHz) δ 158.9 (d, 1JC,F = 240.8 Hz), 155.1, 142.1, 134.8, 128.6, 127.9, 127.2, 121.9 (d, 3JC,F = 8.4 Hz), 115.8 (d, 2JC,F = 22.6 Hz), 75.9,
51.5, 44.2. IR (KBr): ῡ = 3302.39, 2794.53, 2951.98, 1630.84, 1510.68, 1287.08, 834.38. LC-MS for C24H24FN3O: m/z = 390 [M+H]+.
4.2.1.10. Synthesis of N-(4-fluorophenyl)-4-((4-fluorophenyl)(phenyl)methyl)piperazine-1-carboxamide (3j)
Compound (3j) was synthesized from 4-fluorophenyl isocyanate (0.25 g, 1.823 mmol) and 1-((4-fluorophenyl)
(phenyl)methyl)piperazine (0.49 g, 1.823 mmol) according to the general procedure. White solid. Yield = 74% (0.549g). 1H NMR (CDCl3,
500 MHz) δ 7.40-7.37 (m, 4H), 7.31-7.27 (m, 3H), 7.25-7.20 (m, 2H), 7.00-6.94 (m, 4H), 6.31 (s, 1H), 4.25 (s, 1H), 3.47 (t, J = 4.5 Hz,
4H), 2.42 (t, J = 3.0 Hz, 4H). 13C NMR (CDCl3, 125 MHz) δ 160.89, 158.9 (d, 1JC,F = 240.8 Hz), 155.1, 141.9, 137.9, 134.8, 129.3 (d,
3JC,F = 7.3 Hz), 128.7, 127.3, 122.0, 121.9, 115.5 (d, 2JC,F = 21.4 Hz), 115.4 (d, 2JC,F = 22.6 Hz), 75.1, 51.4, 44.2. IR (KBr): ῡ = 3311.8,
2793.8, 2951.8, 1633, 1509, 1209.9, 835.8. LC-MS for C24H23F2N3O: m/z = 408 [M+H]+.
4.2.1.11. Synthesis
of
N-(4-fluorophenyl)-4-((2-fluorophenyl)(4-fluorophenyl)methyl)piperazine-1-
carboxamide (3k)
Compound (3k) was synthesized from 4-fluorophenyl isocyanate (0.25 g, 1.823 mmol) and 1-((2-fluorophenyl)(4-
fluorophenyl)methyl)piperazine (0.525 g, 1.823 mmol) according to the general procedure. White solid. Yield = 70% (0.543g). 1H NMR
(DMSO-d6, 500 MHz) δ 8.55 (s, 1H), 7.64 (t, J = 7.0 Hz, 1H), 7.46-7.43 (m, 4H), 7.29-7.21 (m, 2H), 7.17-7.11 (m, 3H), 7.05 (t, J = 9.0
Hz, 2H), 4.71 (s, 1H), 3.47 (s, 4H), 2.35-2.28 (m, 4H). 13C NMR (DMSO-d6, 125 MHz) δ 160.2, 160.0 (d, 1JC,F= 242.0 Hz), 158.3,
2
2
156.4, 155.0, 137.2, 136.8, 129.7, 128.9, 128.7, 124.8, 121.4, 121.3, 115.7, 115.4 (d, JC,F = 21.5 Hz), 114.8 (d, JC,F = 22.6 Hz), 65.7,
51.2, 43.8. IR (KBr): ῡ = 3307, 2814.18, 1628.47, 1506.23, 1223.83, 816.77. LC-MS for C24H22F3N3O: m/z = 426 [M+H]+.
4.2.1.12. Synthesis of 4-(dibenzo[b,f][1,4] thiazepin-11-yl)-N-(4-fluorophenyl)piperazine-1-carboxamide
(3l)
Compound (3l) was synthesized from 4-fluorophenyl isocyanate (0.25 g, 1.823 mmol) and 11-piperazin-1-yl-dibenzo
[b,f][1,4]thiazepine (0.538 g, 1.823 mmol) according to the general procedure. White solid. Yield = 71% (0.56 g). 1H NMR (DMSO-d6,
500 MHz) δ 8.64 (s, 1H), 7.58-7.55 (m, 1H), 7.49-7.45 (m, 5H), 7.39 (dd, , J = 7.5, 2.0 Hz, 1H), 7.20 (td, J = 7.5, 1.0 Hz, 1H), 7.11-7.05
(m, 2H), 7.03 (dd, J = 7.8, 1.5 Hz, 1H), 6.91 (td, J = 7.5, 1.0 Hz, 1H), 3.61-3.39 (m, 8H). 13C NMR (DMSO-d6, 125 MHz) δ 160.1, 158.4,
156.5, 155.2, 148.5, 138.7, 136.7, 133.4, 132.1, 132.0, 131.4, 129.3, 129.1, 129.0, 128.2, 127.3, 125.1, 122.8, 121.5 (d, 3JC,F = 8.3 Hz),
114.8 (d, 2JC,F = 22.6 Hz), 43.4. IR (KBr): ῡ = 3342.7, 2859.21, 2892.1, 1641.98, 1508.33, 1240.54, 812.81. LC-MS for C24H21FN4OS:
m/z = 433 [M+H]+.
4.2.1.13. Synthesis of 4-benzhydryl-N-(3,4-dichlorophenyl)piperazine-1-carboxamide (3m)
Compound (3m) was synthesized from 3,4-dichlorophenyl isocyanate (0.25 g, 1.329 mmol) and 1-benzhydrylpiperazine (0.335 g,
1
1.329 mmol) according to the general procedure. White solid. Yield = 74% (0.433 g). H NMR (DMSO-d6, 500 MHz) δ 8.76 (s, 1H),
7.82 (d, J = 2.0 Hz, 1H), 7.46-7.41 (m, 6H), 7.3 (t, J = 8.0 Hz, 4H), 7.25-7.14 (m, 2H), 4.34 (s, 1H), 3.47 (t, J = 4.5 Hz, 4H), 2.33-2.29
(m, 4H). 13C NMR (DMSO-d6, 125 MHz) δ 154.4, 142.5, 140, 130.6, 130.1, 128.6, 127.6, 127.0, 122.9, 120.4, 119.2, 74.7, 51.3, 43.8. IR
(KBr): ῡ = 3258.54, 2814.75, 2953, 1642.66, 1505.68, 1245.13, 823.55. LC-MS for C24H23Cl2N3O: m/z = 441 [M+H]+.
4.2.1.14. Synthesis of N-(3,4-dichlorophenyl)-4-((4-fluorophenyl)(phenyl)methyl)piperazine-1-carboxamide
(3n)
Compound (3n) was synthesized from 3,4-dichlorophenyl isocyanate (0.25 g, 1.329 mmol) and 1-((4-fluorophenyl)
(phenyl)methyl)piperazine (0.36 g, 1.329 mmol) according to the general procedure. White solid. Yield = 76% (0.46 g). 1H NMR (DMSO-
d6, 500 MHz) δ 8.83 (s, 1H), 7.83 (s, 1H), 7.47-7.41 (m, 6H), 7.31 (t, J = 7.5 Hz, 2H), 7.20 (t, J = 7.0 Hz, 1H), 7.13 (t, J = 8.5 Hz, 2H),
4.38 (s, 1H), 3.47 (s, 4H), 2.30 (s, 4H). 13C NMR (DMSO-d6, 125 MHz) δ 161.1 (d, 1JC,F = 240.9 Hz), 154.4, 142.2, 140.9, 138.6, 130.5,
130.1, 129.5 (d, 3JC,F = 8.4 Hz), 128.6, 127.6, 127.0, 122.8, 120.3, 119.2, 115.3 (d, 2JC,F = 21.4 Hz), 73.7, 51.2, 43.8. IR (KBr): ῡ = 3301.2,
2791.11, 2952.46, 1637.27, 1505, 1239.68, 823.96. LC-MS for C24H22Cl2FN3O: m/z = 459 [M+H]+.