10.1002/chem.202003315
Chemistry - A European Journal
FULL PAPER
added copper (II) sulfate dissolved in water (0.5 M, 1 mol %) and
aqueous sodium ascorbate (0.1 M, 10 mol %). The reaction
mixture was stirred at room temperature and reaction progress
was monitored by TLC. Upon completion (1 h), the ethanol was
removed under reduced pressure and the residue was dissolved
ethyl acetate (20 mL) and washed H2O (5 mL), with brine (5 mL).
The organic fraction was separated, dried over anhydrous MgSO4
and evaporated under reduced pressure. The crude product was
purified by flash column chromatography using a mixture of 2-5 %
MeOH in CH2Cl2 as eluent to furnish pure title compound 5 as
white solid in 82.5 % yield. 1H-NMR (DMSO-d6, 600 MHz) δ 1.13
(t, J = 7.2 Hz, 6 H, 2 x CH3), 2.30 (s, 3 H, CH3), 3.48 (q, J = 7.2
Hz, 4 H, 2 x CH2), 4.20 (s, 2 H, CH2), 6.64 (d, J = 1.8 Hz, 1 H, Ar-
H), 6.82 (dd, J = 9.0 Hz, J = 1.8 Hz, 1 H, coumarin-ring- H), 7.18
(s, 1 H, CH of pyrazole ring), 7.19 (d, J = 8.4 Hz, 2 H, Ar-H), 7.21
(d, J = 8.4 Hz, 2 H, Ar-H), 7.52 (d, J = 8.4 Hz, 2 H, Ar-H), 7.41 (d,
J = 9.0 Hz, 1 H, coumarin-ring- H), 7.83 (d, J = 8.4 Hz, 2 H, Ar-H),
8.32 (s, 1 H, coumarin-ring- H), 8.38 (s, 1 H), 8.43 (broad s, 1 H,
NH); 13C NMR (DMSO-d6, 150 MHz): δ 12.76 (2 x CH3), 21.38
(CH3), 38.39 (CH2), 44.69 (2 x CH2), 96.84 (coumarin-ring),
106.64 (CH of pyrazole ring), 106.91 (coumarin-ring-Ar-CH),
110.10 (coumarin-ring-Ar-CH), 118.19, 121.11 (q, 1JC-F = 267 Hz,
CF3), 124.59 (coumarin-ring-Ar-CH), 125.4 (C), 125.59 (Ar-CH),
126.50 (C), 128.21 (Ar-CH), 129.14 (Ar-CH), 129.91 (Ar-CH),
130.94 (coumarin-ring-Ar-CH), 130.12 (C), 137.00, 139.56,
141.99, 143.82 (q, 2J = 36 Hz, pyrazole C3), 145.70, 151.91,
156.08, 157.09; 19F (DMSO-d6, 565 MHz): -60.90 (CF3); EI-MS:
678.7 [M+H]+; Anal. Calculated for C33H30F3N7O4S: C, 58.49; H,
4.46; N, 14.47; S, 4.73; found: C, 58.42; H, 4.48; N, 14.49; S, 4.68.
the ethanol was removed under reduced pressure and the residue
was dissolved ethyl acetate (20 mL) and washed H2O (5 mL), with
brine (5 mL). The organic fraction was separated, dried over
anhydrous MgSO4 and evaporated under reduced pressure. The
crude product was purified by flash column chromatography using
a mixture of 2-5 % MeOH in CH2Cl2 as eluent to furnish pure title
1
compound 12 in 85 % yield as a white solid. H-NMR (CD3OD,
600 MHz) δ 2.23 (s, 3 H, CH3), 2.80-2.91 (m, 2H, CH2), 3.24-3.28
(m, 2 H, CH2), 4.32-4.37 (m, 2 H, CH2), 4.36 (s, 2 H, CH2), 6.38
(d, J = 9.0 Hz, 1 H, NBD-ring), 6.86 (s, 1 H, CH of pyrazole ring),
7.02-7.07 (m, 4H, Ar-H), 7.35-7.41 (m, 2 H, Ar-H), 7.65-7.72 (m,
2 H, Ar-H), 7.85 (s, 1 H), 8.34 (d, J = 9.0 Hz, NBD-ring); 13C NMR
(CD3OD, 150 MHz):19.86 (CH3), 29.41 (CH2), 39.26 (CH2), 43.31
(CH2), 51.21 (CH2), 105.51 (CH of pyrazole ring), 121.04 (q, 1JC-F
= 267 Hz, CF3), 122.30 (C-NO2), 123.82 (NBD-ring CH), 125.69
(C), 125.88 (Ar-CH), 127.51 (Ar-CH), 128.69 (Ar-CH), 129.29 (Ar-
CH), 131.41, 132.38 (C), 134.48 (C), 136.89 (NBD-ring CH),
139.66 (C), 140.39, 142.39, 143.69, 144.07 (q, 2J = 36 Hz,
pyrazole C3),144.65, 145.78; 19F (CD3OD, 565 MHz): -63.91
(CF3); EI-MS: 683.1 [M+H]+; Anal. Calculated for C29H25F3N10O5S:
C, 51.03; H, 3.69; N, 20.52; S, 4.70; found: C, 51.08; H, 3.62; N,
20.59; S, 4.78.
Synthesis of N-(2-(4-(((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-
amino)methyl)-2H-1,2,3-triazol-2-yl)ethyl)-4-(5-(p-tolyl)-3-(tri-
fluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide 15: N-(2-
Azidoethyl)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-
benzenesulfonamide 14 (200 mg, 0.44 mmol) and 7-nitro-N-
(prop-2-yn-1-yl)benzo[c][1,2,5]oxadiazol-4-amine 11 (96 mg 0.44
mmol) and were stirred together in ethanol and water (v/v = 2:1,
5 mL). To this reaction mixture was added copper (II) sulfate
dissolved in water (0.5 M, 1 mol %) and aqueous sodium
ascorbate (0.1 M, 10 mol %). The reaction mixture was stirred at
room temperature and reaction progress was monitored (TLC).
Upon completion (1 h), the ethanol was removed under reduced
pressure and the residue was dissolved ethyl acetate (20 mL) and
washed H2O (5 mL), with brine (5 mL). The organic fraction was
separated, dried over anhydrous MgSO4 and evaporated under
reduced pressure. The crude product was purified by flash column
chromatography using a mixture of 2-5 % MeOH in CH2Cl2 as
eluent to furnish pure title compound 15 in 88.5 % yield as a white
solid. 1H-NMR (CD3OD, 600 MHz) δ 2.23 (s, 3 H, CH3), 3.27-3.29
(m, 2 H, HN-CH2-CH2), 4.36-4.38 (m, 2 H, HN-CH2-CH2), 4.39 (s,
2 H, CH2), 6.33 (d, J = 9.0 Hz, 1 H, NBD-ring), 6.81 (s, 1 H, CH of
pyrazole ring), 7.04-7.09 (m, 4H, Ar-H), 7.38-7.40 (m, 2 H, Ar-H),
7.69-7.71 (m, 2 H, Ar-H), 7.86 (s, 1 H), 8.39 (d, J = 9.0 Hz, NBD-
ring); 13C NMR (CD3OD, 150 MHz):19.86 (CH3), 37.23 (CH2),
42.35 (CH2), 52.23 (CH2), 105.58 (CH of pyrazole ring), 121.06 (q,
1JC-F = 267 Hz, CF3), 122.34 (C-NO2), 123.88 (NBD-ring CH),
125.68 (C), 125.81 (Ar-CH), 127.59 (Ar-CH), 128.64 (Ar-CH),
129.23 (Ar-CH), 131.43, 132.31 (C), 134.43 (C), 136.81 (NBD-
ring CH), 139.66 (C), 140.31, 142.33, 143.63, 144.01 (q, 2J = 36
Synthesis of N-((1-(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-1H-
1,2,3-triazol-4-yl)methyl)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-
pyrazol-1-yl)benzenesulfonamide 7: 4-Azido-7-nitrobenzo-
[c][1,2,5]oxadiazole (6, 124 mg, 0.6 mmol) and N-(prop-2-yn-1-
yl)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzene-
sulfonamide 3 (251 mg, 0.6 mmol) were stirred together in ethanol
and water (v/v = 2:1, 5 mL). To this reaction mixture was added
copper(II)sulfate dissolved in water (0.5 M, 1 mol %) and aqueous
sodium ascorbate (0.1 M, 10 mol %). The reaction mixture was
stirred at room temperature and reaction progress was monitored
by TLC. Upon completion (1 h), the ethanol was removed under
reduced pressure and the residue was dissolved ethyl acetate (20
mL) and washed H2O (5 mL), with brine (5 mL). The organic
fraction was separated, dried over anhydrous MgSO4 and
evaporated under reduced pressure. The crude product was
purified by flash column chromatography using a mixture of 2-5 %
MeOH in CH2Cl2 as eluent to furnish pure title compound 7 in 84.5
yield. 1H-NMR (CDCl3, 600 MHz) δ 2.36 (s, 3 H, CH3), 4.47 (s, 2
H, CH2), 6.84 (s, 1 H, CH of pyrazole ring), 7.14 (d, J = 8.4 Hz, 2
H, Ar-H), 7.21(d, J = 8.4 Hz, 2 H, Ar-H), 7.36 (d, J = 8.4 Hz, 2 H,
Ar-H), 7.83 (d, J = 8.4 Hz, 2 H, Ar-H), 8.38 (d, J= 7.8 Hz, 1 H, Ar-
H), 8.72 (s, 1 H), 8.76 (d, J = 7.8, 1 H, Ar-H); 13C NMR (CDCl3,
150 MHz): 21.17 (CH3), 41.71 (CH2), 106.35 (CH of pyrazole ring), Hz, pyrazole C3),144.60, 145.73; 19F (CD3OD, 565 MHz): -63.91
1
117.45, 119.48, 120. 52, 121.13 (q, JC-F = 267 Hz, CF3), 125.4
(Ar-CH), 125.7 (4-methylphenyl C1), 128. 4 (Ar-CH), 128.7 (Ar-
CH), 129.7 (Ar-CH), 131.81, 132.45, 135.4, 139.2, 139.8, 142.6,
(CF3); EI-MS: 669.6 [M+H]+; Anal. Calculated for C28H23F3N10O5S:
C, 50.30; H, 3.47; N, 20.95; S, 4.80; found: C, 50.28; H, 3.42; N,
20.91; S, 4.84.
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143.11, 143.4 (q, J = 36 Hz, pyrazole C3), 145.2, 149.54; 19F
Synthesis of NBD-DBCO 17: Into a solution of 4-chloro-7-
nitrobenzo[c][1,2,5]oxadiazole 10 (200 mg, 1 mmol) in 10 mL dry
THF, DBCO-amine 16 (276 mg, 1 mmol) and dry triethylamine
(1 mmol) were added. The reaction mixture was stirred at 25 °C,
and the progress was monitored by TLC, upon completion (1 h),
the solvent was evaporated in reduced pressure, and the residue
was dissolved CH2Cl2 and the organic fraction was washed with
brine and then dried over anhydrous Na2SO4 and evaporated
under reduced pressure. The crude product was purified by flash
column chromatography using a mixture of 2-5 % MeOH in
CH2Cl2 as eluent to furnish pure compound 17 in 88% yield as a
thick liquid. 1H NMR (CDCl3, 600 MHz): δ 2.28 (ddd, J = 15.6 Hz,
J = 8.1 Hz, J = 4.2 Hz, 1 H of CH2), 2.54 (ddd, J = 15.6 Hz, J =
8.1 Hz, J = 4.2 Hz, 1 H of CH2), 3.41-3.45 (m, 2 H, CH2), 3.61 (d,
J = 13.8 Hz, 1 H of CH2), 5.08 (d, J = 13.8 Hz, 1 H of CH2), 5.84
(CDCl3, 565 MHz,): -62.19 (CF3); EI-MS: 626.5 [M+H]+; Anal.
Calculated for C26H18F3N9O5S: C, 49.92; H, 2.90; N, 20.15; S, 5.13,
found: C, 49.90; H, 2.96; N, 20.11; S, 5.09.
Synthesis of N-(3-(4-(((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)-
amino)methyl)-1H-1,2,3-triazol-1-yl)propyl)-4-(5-(p-tolyl)-3-
(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide 12: N-
(3-Azidopropyl)-4-(5-(p-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)-
benzenesulfonamide 9 (200 mg, 0.44 mmol) and 7-nitro-N-(prop-
2-yn-1-yl)benzo[c][1,2,5]oxadiazol-4-amine 11 (0.44 mmol) and
were stirred together in ethanol and water (v/v = 2:1, 5 mL). To
this reaction mixture was added copper (II) sulfate dissolved in
water (0.5 M, 1 mol %) and aqueous sodium ascorbate (0.1 M, 10
mol %). The reaction mixture was stirred at room temperature and
reaction progress was monitored by TLC. Upon completion (1 h),
7
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