Molecules 2021, 26, 1653
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3.1.6. General Procedure of Coumarin-3-carboxamides Preparation (14a–g)
Triethanolamine (TEA) (0.1 mL, 1.36 mmol) was added to a solution of compound 13
(70 mg, 0.26 mmol) and HATU (0.12 g, 0.36 mmol) in dry THF (5 mL), and the mixture was
stirred at room temperature for 30 min. The obtained dark clear mixture was treated with
aniline derivatives (11a
for 18 h. Dichloromethane (50 mL) was added, and the resulting solution was extracted
with sat. NaCl (3 30 mL). The remaining organic layer was dried over Na2SO4 before
–g) (1.2 eq.). The resulting mixture was stirred at room temperature
×
evaporation to dryness. After evaporation of the solvent in vacuo, the crude product was
purified via preparative thin-layer chromatography (silica gel, 4:1 hexane:EtOAc) to give
yellow solids of coumarin-3-carboxamide (14a–g)
7-Hydroxy-6-(3-methylbut-2-en-1-yl)-2-oxo-N-phenyl-2H-chromene-3-carboxamide
◦
1
14a (47 mg, 51% yield): m.p. 258–259 C, H NMR (300 MHz, CDCl3+pyridine-d5):
δ
10.86 (s, NH), 8.90 (s, 1H), 7.73 (d, J = 7.62 Hz, 2H), 7.42 (s, 1H), 7.35 (t, J = 7.62 Hz, 2H), 7.12
(t, J = 7.38 Hz, 1H), 6.84 (s, 1H), 5.40 (tt, J = 7.26, 1.35 Hz, 1H), 3.43 (d, J = 7.26 Hz, 2H), 1.81
(s, 3H), 1.74 (s, 1H) ppm., 13C NMR (75 MHz, CDCl3+pyridine-d5):
δ 163.38 (C), 162.81 (C),
160.56 (C), 155.49 (C), 149.36 (CH), 138.08 (CH), 134.13(C), 130.04 (CH), 128.97 (2CH), 128.68
(C), 124.35 (CH), 121.14 (CH), 120.49 (2CH), 112.94 (C), 111.33 (C), 101.68 (CH), 27.85 (CH2),
25.84 (CH3), 17.85 (CH3) ppm., IR: 3195.27 (O-H), 2917.31 (C-H, aliphatic), 1695.54 (C=O,
amide) cm−1; HREI-MS (m/z) calculated for C21H20O4N (M)+ 350.1387, found 350.1386.
N-(4-Fluorophenyl)-7-hydroxy-6-(3-methylbut-◦2-en-1-yl)-2-oxo-2H-chromene-3-car-
1
boxamide 14b (45 mg, 47% yield): m.p. 259–261 C, H NMR (300 MHz, CDCl3):
δ
10.56 (br, NH), 8.89 (s, 1H), 7.68 (dd, J = 8.97, 4.92 Hz, 2H), 7.42 (s, 1H), 7.07 (dd, J = 9.12,
8.79 Hz 2H), 6.83 (s, 1H), 5.34 (t, J = 7.23 Hz, 1H), 3.35 (d, J = 7.29 Hz, 2H), 1.80 (s, 3H), 1.72
(s, 1H) ppm., 13C NMR (75 MHz, CDCl3):
δ 163.04 (C), 162.57 (C), 160.72 (C), 159.64 (d,
J = 242.5 Hz, C), 155.46 (C), 149.71 (CH), 134.43 (C), 133.84 (d, J = 3.0 Hz, C), 130.23 (CH),
128.80 (C), 120.91 (CH), 115.72 (d, J = 22.5 Hz, 2CH), 112.86 (C), 112.31 (d, J = 7.5 Hz, 2CH),
111.68 (C), 101.70 (CH), 27.74 (CH2), 25.87 (CH3), 17.82 (CH3) ppm., 19F NMR (282 MHz,
CDCl3, std. TFA):
−
118.08 (s, 1F) ppm., IR: 3208.66 (O-H), 3155.21 (N-H), 3048.54 (C-H,
aromatic), 2913.86 (C-H, aliphatic), 1698.12 (C=O, amide) cm−1; HREI-MS (m/z) calculated
for C21H19O4NF (M)+ 368.1293, found 368.1293.
N-(4-Chlorophenyl)-7-hydroxy-6-(3-methylbut-2-en-1-yl)-2-oxo-2H-chromene-3-car-
boxamide 14c (44 mg, 44% yield): m.p. 282–283 ◦C, 1H NMR (300 MHz, CDCl3+pyridine-
d5):
2.01 Hz, 2H), 6.83 (s, 1H), 5.41 (t, J = 7.23 Hz, 1H), 3.43 (d, J = 7.23 Hz, 2H), 1.81 (s, 3H), 1.74
(s, 1H) ppm., 13C NMR (75 MHz, CDCl3+pyridine-d5):
163.65 (C), 162.81 (C), 160.64 (C),
δ 10.92 (s, NH), 8.89 (s, 1H), 7.69 (d, J = 8.88 Hz, 2H), 7.37 (s, 1H), 7.30 (dd, J = 8.89,
δ
155.57 (C), 149.50 (CH), 136.76 (C), 134.06 (C), 130.09 (CH), 129.15 (C), 128.95 (2CH), 128.83
(C), 121.64 (2CH), 121.17 (CH), 112.56 (C), 111.27 (C), 101.68 (CH), 27.85 (CH2), 25.83 (CH3),
17.84 (CH3) ppm. IR: 3196.03 (O-H), 3122.34 (N-H), 3073.18 (C-H, aromatic), 2911.85 (C-H,
aliphatic), 1698.47 (C=O, amide) cm−1; HREI-MS (m/z) calculated for C21H19O4N35Cl (M)+
384.0997, found 384.0996.
N-(4-Bromophenyl)-7-hydroxy-6-(3-methylbut-2-en-1-yl)-2-oxo-2H-chromene-3-car-
◦
boxamide 14d (52 mg, 47% yield)): m.p. 276–277 C, 1H NMR (300 MHz, CDCl3+pyridine-
d5):
1H), 6.83 (s, 1H), 5.40 (t, J = 7.14 Hz, 1H), 3.43 (d, J = 7.26 Hz, 2H), 1.81 (s, 3H), 1.73 (s, 1H)
ppm., 13C NMR (75 MHz, CDCl3+pyridine-d5):
163.67 (C), 162.80 (C), 160.65 (C), 155.57
δ 10.92 (s, NH), 8.89 (s, 1H), 7.69 (d, J = 8.88 Hz, 2H), 7.44 (d, J = 9.66 Hz, 2H), 7.39 (s,
δ
(C), 149.51 (CH), 137.25 (C), 134.04 (C), 131.89 (2CH), 130.09 (CH), 128.83 (C), 121.96 (2CH),
121.16 (CH), 116.80 (C), 112.52 (C), 111.25 (C), 101.67 (CH), 27.85 (CH2), 25.83 (CH3), 17.84
(CH3) ppm. IR: 3192.94 (O-H), 3070.45 (C-H, aromatic), 2915.14 (C-H, aliphatic), 1697.23
(C=O, amide) cm−1; HREI-MS (m/z) calculated for C21H19O4N79Br (M)+ 428.0492, found
428.0492.
N-(2,5-Difluorophenyl)-7-hydroxy-6-(3-methylbut-2-en-1-yl)-2-oxo-2H-chromene-3-
◦
carboxamide 14e (46 mg, 46% yield): m.p. 248–250 C, 1H NMR (300 MHz, CDCl3+pyridine-
d5):
δ 12.27 (s, NH), 8.90 (s, 1H), 8.40 (ddd, J = 10.46, 6.66, 3.15 Hz, 1H), 7.43 (s, 1H), 7.04
(ddd, J = 9.57, 9.18, 4.89 Hz, 1H), 6.86 (s, 1H), 6.65–6.75 (m,1H), 5.41 (t, J = 7.35 Hz, 1H), 3.43