GHALEHSHAHI ET AL.
11 of 14
|
4-Aminocoumarin (1d)[26]
Yield: 151 mg (94%), yellow solid. m.p.: 160–161°C, IR cm−1 (KBr):
H-Ar), 8.17 (d, 2H, J = 7.3 Hz, H-Py). 13C NMR (75 MHz, DMSO-d6): δ
(ppm) = 114.1, 115.6, 124.0, 125.4, 126.2, 129.3, 133.7, 140.5, 141.7,
151.8, 153.4, 159.6. HR-MS (ESI, 0.5 eV) m/z = calcd. for C14H11N2O2
[M+H]+ = 239.0820, found = 239.0820.
1
1670, 3222, 3397. H (300 MHz, CDCl3): δ (ppm) = 5.21 (s, 1H, CH),
7.27–7.31 (m, 2H, H-Ar), 7.38 (brs, 2H, NH2), 7.55–7.60 (m, 1H, H-Ar),
7.97 (d, 1H, J = 7.8, 1H Hz). 13C NMR (75 MHz, CDCl3): δ (ppm) = 83.8,
114.4, 116.8, 123.0, 123.2, 132.1, 153.7, 155.6, 161.6. LC-MS (UPLC-
TOF) m/z = calcd. for C9H7NO2 [M] = 161.0476, found = 161.04747.
Calcd. for C9H8NO2 [M+H]+ = 162.0553, found = 162.0553.
3-(Pyridin-4-ylamino)-2H-chromen-2-one (2c)
Yield: 200 mg (84%), yellow powder. IR cm−1 (KBr): 1265, 1704, 3056.
1H NMR (300 MHz, DMSO-d6): δ (ppm) = 7.26 (d, 2H, J = 4.4 Hz, H-Py),
7.33 (td, 1H, J = 7.3, 1.5 Hz, H-Ar), 7.40 (t, 1H, J = 6.9 Hz, H-Ar), 7.46
(t, 1H, J = 8.5 Hz, H-Ar), 7.68 (dd, 1H, J = 7.7, 1.5 Hz, H-Ar), 7.80 (s, 1H,
|
4.1.5 Synthesis of 4-hydrazinocoumarin (1e)
CH), 8.33 (d, 2H, J = 5.4 Hz, H-Py), 8.73 (s, NH). 13C (75 MHz,
Well-powdered 4-hydroxycoumarin (1 mmol, 162 mg) and hydrazine
hydrate (0.5 mL) were refluxed for 2 h. The solvent was removed under
reduced pressure. Cold water (5 mL) was added to the obtained orange
oil, resulting in white participates, which were then recrystallized in
ethanol.
DMSO-d6): δ (ppm) = 111.8, 115.7, 118.1, 120.0, 124.8, 126.6, 127.1,
128.5, 148.2, 149.2, 150.2, 158.4. HR-MS (ESI, 0.5 eV) m/z = calcd. for
C14H11N2O2 [M+H]+ = 239.0820, found = 239.0820.
|
4.1.7 General procedure for the synthesis of amino
acid methyl ester[27]
4-Hydrazinocoumarin (1e)[43]
Yield: 160 mg (91%), white solid, m.p.: 178–180°C. 1H NMR (300 MHz,
Amino acid (1 mmol) was added to methanol (2 mL), and then, the flask
was cooled in an ice bath for 1–2 min. Thionyl chloride (2 mmol) was
injected slowly into the amino acid–methanol mixture. The mixture
was then stirred overnight at room temperature. After the completion
of the reaction, the solvent was evaporated and washed with Et2O to
yield a white solid precipitate as amino acid methyl ester hydrochloric
acid salt (yield 95%).
DMSO-d6): δ (ppm) = 3.3 (brs, 2H, NH2), 5.91 (s, 1H, CH), 6.80–6.89
(m, 2H, H-Ar), 708–7.14 (m, 1H, H-Ar), 7.56 (dd, 1H, J = 7.9, 1.7 Hz,
H-Ar), 9.25 (s, 1H, NH), 5.94 (s, 1H, CH), 6.84 (t, 1H, J = 7.5 Hz, H-Ar),
6.90 (d, 1H, J = 8.1 Hz, H-Ar), 7.11 (t, 1H, J = 8.5 Hz, H-Ar), 7.56 (dd, 1H,
J = 7.9, 1.7 Hz, H-Ar), 10.88 (s, NH, NH2). 13C NMR (75 MHz, DMSO-
d6): δ (ppm) = 116.4, 117.1, 119.2, 126.8, 128.7, 155.0. HR-MS (EI,
70 eV) = calcd. for C9H9N2O2 [M+H]+ = 177.0664, found = 177.0663.
|
4.1.8 Synthesis of compounds 3a–c
|
4.1.6 Synthesis of 4-(pyridin-4-ylamino)pyridin-1-
For preparation of 2-oxo-2H-chromen-4-yl 4-methylbenzenesulfo-
nate, Et3N (37 mmol, 5.2 mL) was slowly added to 4-hydroxycoumarin
(31 mmol, 5.0 g) in dichloromethane (150 mL). Then, 4-methylbenze-
nesulfonyl chloride (37 mmol, 7.0 g) was slowly added to the solution,
which was stirred in an ice bath. A light yellow solution was obtained
and stirred for 4 h at room temperature until it turned light orange. The
progress of the reaction was monitored through TLC (EtOAc/n-hexane
1:4). The solvent was then evaporated under vacuum, and the
remaining mixture was washed with 1 N HCl (50 mL) and extracted
with chloroform (100 mL) three times. A white solid was obtained
(yield 94%) after solvent evaporation.
ium chloride (2a)
A mixture of absolute EtOH (2 mL), potassium carbonate (0.5 mmol,
69 mg), 4-chloropyridine hydrochloride (1 mmol, 150 mg) and 4-
aminopyridine was refluxed for 3 h. The reaction mixture was
concentrated to residue and recrystallized in (EtOH/EtOAc, 1:1). A
colorless product was identified. A similar method was followed to
synthesize 2b and 2c using 4-aminocoumarin and 3-aminocoumarin
instead of 4-aminopyridine, in that order.
4-(Pyridin-4-ylamino)pyridin-1-ium chloride (2a)[44]
Yield: 155 mg (75%), yellow powder. m.p.: 180°C decompose; IR cm−1
A 10 mL flask equipped with a stirrer and a condenser was charged
with amino acid hydrochloric methyl ester (1.2 mmol), 4-tosyl
coumarin (316 mg, 1 mmol), triethylamine (TEA, 1.2 mmol, 121 mg),
and ACN (acetonitrile, 1 mL). The reaction mixture was stirred at
80°C for 5 h and then evaporated under reduced pressure. The crude
residue was purified through flash chromatography.
(KBr): 1668, 3317, 3435. 1H NMR (300 MHz, DMSO-d6):
δ
(ppm) = 7.12 (d, 2H, J = 7.2 Hz, H-Py), 7.79 (d, 2H, J = 5.3 Hz, H-Py),
8.59 (d, 2H, J = 7.2 Hz, H-Py), 8.82 (d, 2H, J = 5.4 Hz, H-Py), 9.26 (brs,
1H, −NH). 13C NMR (75 MHz, DMSO-d6): δ (ppm) = 109.8, 117.2,
141.0, 148.2, 151.6, 159.9. HR-MS (ESI, 0.5 eV) m/z = calcd. for
C
10H10N3 [M+H]+ = 172.0875, found = 172.0875.
Methyl (2-oxo-2H-chromen-4-yl)-L-tyrosinate (3a)[43]
4-(Pyridin-4-ylamino)-2H-chromen-2-one (2b)
Yield: 309 mg (91%), white solid, [α]20D = −12 (C = 1, EtOAc). IR cm−1
(KBr): 1614, 1747, 3309; 1H NMR (300 MHz, DMSO-d6):
δ
Yield: 223 mg (94%), yellow powder. m.p.: 210–213°C. IR cm−1 (KBr):
1380, 1633, 1727, 3443. 1H NMR (300 MHz, DMSO-d6): δ (ppm) = (s,
(ppm) = 3.21 (d, 2H, J = 7.9 Hz, −CH2), 3.66 (s, 3H, OMe), 4.49 (td,
3
3H, 3.31 (s, 1H, NH), 7.02 (s, 1H, CH), 7.07 (d, 1H, J = 7.2 Hz, H-Py),
1H, J = 8.3, 6.4 Hz, −CH sp ), 5.09 (s, 1H, CH), 6.64 (d, 2H, J = 8.4 Hz,
7.34 (d, J = 8.0 Hz, 1H, H-Ar), 7.42 (t, 1H, J = 7.6 Hz, H-Ar), 7.59 (d, 1H,
H-Ar), 7.13 (d, 2H, J = 8.4 Hz, H-Ar), 7.30 (d, 1H, J = 8.7 Hz, H-Ar), 7.35
J = 8.3 Hz, H-Ar), 7.74 (d, 2H, J = 8.0 Hz, H-Ar), 7.78 (t, 1H, J = 6.9 Hz,
(t, J = 8.0, 1H, H-Ar), 7.69 (d, 1H, J = 8.2 Hz, H-Ar), 8.16 (dd, 1H, J = 8.2,