SYNTHESIS OF DIHYDROQUINOLINE-BASED DERIVATIVES
357
1
chloride (22 mL), followed by the addition of diiso-
propylethylamine (100 μL, 75 mg, 0.576 mmol,
1.5 equiv), disuccinimidyl carbonate (117 mg,
0.456 mmol, 1.2 equiv), and 4-dimethylaminopyri-
dine (23 mg, 0.19 mmol, 0.5 equiv). The mixture was
stirred at room temperature for 1 h, followed by the
addition of disuccinimidyl carbonate (12 mg) and stir-
ring for another 1.5 h. The mixture was poured into
saturated potassium dihydrogen phosphate (25 mL)
and shaken in a separating funnel. The organic phase
was separated, dried over anhydrous sodium sulfate,
and evaporated in a vacuum. The product was purified
by reverse-phase chromatography using a water–ace-
tonitrile gradient. The product-containing fractions
eluting with 40% acetonitrile were combined and
evaporated to half the volume, extracted with methy-
lene chloride, dried with anhydrous sodium sulfate,
and evaporated in a vacuum. The yield of compound
(VIb) in the form of purple foam was 67 mg (26%). Rf
0.72 (methanol–chloroform, 1 : 3). Mass spectrum,
m/z: found: 688, calc.: 687.3. Maximum absorption
mixture 1 : 1). Н NMR in СDCl3 (500 MHz) δ
(ppm): 8.62 (1H, s, C4'H), 8.19 (1H, d, J = 7.8, C7'H),
7.58 (1H, t, J = 5.6, CONH), 7.20 (1H, d, J = 7.8,
C6'H), 6.72 (2H, s, C12H + C13H), 6.50 (2H, s, C5H +
C7H), 5.32 (2H, s, C3H + C9H), 3.61 (2H, dd, J =
12.6, 6.4, CONHCH2), 3.53 (4H, m, N1CH2CH3 +
N11 CH2CH3), 3.45 (2H, t, J = 6.7, CH2N3), 1.97 (2H,
qt, J = 6.7, CONHCH2CH2), 1.72 (6H, s, C4–CH3 +
C7–CH3), 1.42 (12H, d, J = 5.3, C2–2*CH3 + C10–
2*CH3), 1.34 (6H, m, N1CH2CH3 + N11CH2CH3).
6-Sy630-N3
4-((3-Azidopropyl)carbamoyl)-2-
(1,11-diethyl-2,2,4,8,10,10-hexamethyl-10,11-dihy-
dro-2H-pyrano[3,2-g:5,6-g']diquinolin-1-ium-6-yl)-
benzoate (VIIb). 6-Sy630-NHS (66 mg, 0.096 mmol)
was dissolved in dry methylene chloride (10 mL), fol-
lowed by the addition of 3-aminopropylazide (19 mg,
0.192 mmol, 2 equiv). The mixture was stirred at room
temperature for 4 h, diluted with methylene chloride
(10 mL), and washed with 0.1% trifluoroacetic acid
(2 × 10 mL), sodium bicarbonate (saturated solution–
water, 1 : 1; 2 × 10 mL), and saturated solution of
sodium chloride (20 mL). The product was purified by
silica gel chromatography eluting with 5% ethanol in
chloroform containing 1% trimethylamine. The yield
of compound (VIIb) in the form of a blue-purple pow-
der was 41 mg (64%). Rf 0.27 (methanol–chloroform,
1 : 10 with 5% triethylamine). Mass spectrum, m/z:
1
wavelength, 603 nm (in water). Н NMR in СDCl3
(400 MHz) δ (ppm): 8.51 (1H,d, J = 8.2), 8.44 (1H,
dd, J = 8.2, 1.6), 7.99 (1H, d, J =1.5), 6.64 (2H, s),
6.60 (2H, s), 5.46 (2H, s), 3.61–3.64 (4H, m), 2.94
(4H, s), 1.77 (6H, s), 1.48 (12H, d), 1.39 (6H, t, J =
7.0).
5-Sy630-N3
5-((3-Azidopropyl)carbamoyl)-2-
1
found: 673.248, calc.: 672.3. Н NMR in СDCl3
(1,11-diethyl-2,2,4,8,10,10-hexamethyl-10,11-dihy-
dro-2H-pyrano[3,2-g:5,6-g']diquinolin-1-ium-6-yl)-
benzoate (VIIa). 5-Carboxy-Sy630 (0.265 g,
0.45 mmol) was dissolved in dry methylene chloride
(10 mL), followed by the addition of TSTU (0.162 g,
0.54 mmol, 1.2 equiv), diisopropylethylamine (94 μL,
0.54 mmol, 1.2 equiv, 70 mg), and DMAP (27 mg,
0.22 mmol, 0.5 equiv) under stirring. After stirring for
80 min, the mixture was poured into 1% hydrochloric
acid (100 mL). The product was extracted with chlo-
roform (2 × 50 mL), dried over aqueous sodium sul-
fate, and evaporated in a vacuum. The residue was dis-
solved in dry methylene chloride (10 mL), followed by
the addition of aminopropylazide (68 μL, 0.675 mmol,
1.5 equiv) and diisopropylamine (118 μL, 87 mg,
0.675 mmol, 1.5 equiv). The mixture was stirred for
20 min and evaporated in a vacuum. The product was
purified by silica gel chromatography eluting with a
gradient of methanol in chloroform (0–5%) and then
a gradient of methanol in chloroform (6–8%) con-
taining 1% trimethylamine. The solution of the prod-
uct was evaporated in a vacuum and dried over Р2О5.
The yield of compound (VIIa) in the form of purple
powder was 212 mg (70%). Rf 0.54 (methanol–chlo-
roform, 1 : 4). Mass spectrum, m/z: found: 673.423,
calc.: 672.3; quantum yield, 0.74 (in an ethanol–
water mixture 1 : 1); molar absorption coefficient at
(500 MHz) δ (ppm): 8.24 (1H, d, J = 8.1), 8.11 (1H, d,
J = 8.0), 7.75 (2H, s), 6.66 (2H, s), 6.53 (2H, s), 5.35
(2H, s), 3.58 (4H, nonresolved q, J = 6.8, 2*CH2N),
3.50 (2H, dt, J = 15.8, 7.9, CH2NHCO), 2.36 (2H, t,
J = 6.9, CH2N3), 1.92 (2H, qt, J = 6.8, –CH2–), 1.66
(6H, s, 2*CH3), 1.44 (12H, s, 4*CH3), 1.33 (6H, t, J =
6.9, 2*CH2CH3). Based on the HMBC and HSQC
spectrum, the 13C NMR spectrum was correlated, and
the structures of each isomer were confirmed.
13С NMR in СDCl3 (126 MHz) δ (ppm): 166.93
(COO–), 165.61 (CONH), 157.46 (2C, F), 157.29 (2),
151.54 (2C, D), 136.27 (6), 136.10 (1), 133.02 (3),
131.29 (2C, X), 131.18 (1), 128.45 (5), 127.79 (4),
125.41 (2C, E), 123.04 (2C, A), 122.29 (2C, H), 113.63
(2C, C), 94.90 (2C, B), 59.42 (2C, 2*C(CH3)2), 48.96
(a), 39.56 (2C, 2*NCH2CH3), 37.27 (c), 29.22, 29.05
(4C, 4*CH3), 28.16 (b), 17.86 (2*CH3), 12.76
(2*CH2CH3).
2-Amino-4-methoxyacetophenone (VIII). The
solution of m-anisidine (2.777 mL, 24.72 mmol, 3.044 g)
in dry benzene (20 mL) was added dropwise to 1 M
boron trichloride solution (25 mL) under ice-cooling
in an apparatus equipped with a calcium chloride tube,
followed by the addition of acetonitrile (2.58 mL,
49.44 mmol, 3.03 g, 2 equiv) and aluminum chloride
(3.626 g, 27.19 mmol, 1.1 equiv). The mixture was
λ
max, 1.286 × 105 М–1 cm–1; maximum absorption
wavelength, 596 nm (in water); maximum fluores- refluxed for 2 h; methylene chloride was evaporated
cence wavelength, 620 nm (in an ethanol–water with dephlegmator until the temperature reached
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 46 No. 3 2020