M. Reyes-Batlle, et al.
BioorganicChemistry99(2020)103791
(1H, d, J = 9.6 Hz, H-4), 7.66 (1H, d, J = 7.8 Hz, H-8), 7.52 (1H, dd,
J = 7.4, 8.0 Hz), 7.41 (1H, d, J = 8.2 Hz, H-5), 7.20 (1H, dd, J = 7.4,
7.6 Hz), 6.53 (1H, d, J = 9.6 Hz, H-3); 13C NMR (100 MHz, (CD3)2CO)
δ: 163.1 (s, C-2), 141.1 (d), 141.0 (s), 131.3 (d), 128.8 (d), 122.9 (d),
122.8 (d), 120.5 (s), 116.0 (d); EIMS: m/z 146 [M++1] (14), 145 [M]+
(100), 89 (20); HRMS: calcd. for C9H7NO 145.0528, found 145.0525.
(73), 77 (13); HRMS: calcd. for C13H13NO3 231.0895, found 231.0898.
4.2.3.5. 4-[(2-Oxoquinolin-1(2H)-yl)methyl]benzonitrile (8e). From
5
(70.0 mg, 0.48 mmol), anhydrous DMF (2.4 mL), NaH 40% (58.0 mg,
2.41 mmol) and 4-(bromometyl)benzonitrile (0.97 mmol, 189 mg);
stirring for 1 h; column chromatography (hexane/EtOAc, 4:1, 1:1);
product 8e (88.0 mg, 70%) was obtained as a white solid. 1H NMR
(500 MHz, CDCl3) δ: 7.63 (1H, d, J = 9.5 Hz, H-4), 7.58–7.55 (3H, m),
7.42 (1H, td, J = 1.5, 7.2 Hz), 7.29 (2H, d, J = 8.5 Hz), 7.20 (1H, td,
J = 0.8, 8.0 Hz), 7.10 (1H, d, J = 8.5 Hz), 6.77 (1H, d, J = 9.4 Hz, H-
3), 5.57 (2H, s, H-1′).
4.2.3. N-alkyl- and N-benzoylquinolin-2(1H)-one derivatives. General
procedure
To a vigorously stirring solution of 5 in anhydrous DMF at 0 °C was
added NaH (40%) portion wise. After 30–60 min the acylating or al-
kylating agent was added, and the reaction mixture was stirred for 1 h-
5 days at room temperature and under argon, after which H2O was
added and the mixture was lyophilized·H2O (10–15 mL) was added and
the mixture was extracted with EtOAc (3 × 10 mL). The combined
organics phases were washed with brine (10–15 mL), dried (Na2SO4),
filtered and concentrated. Purification using column or preparative thin
layer chromatography (hexane/EtOAc) afforded the desired products.
4.2.3.6. 1-Benzoylquinolin-2(1H)-one (9a). From
7
(51.0 mg,
0.35 mmol), anhydrous DMF (2.8 mL), 40% NaH (42.0 mg,
1.58 mmol) and benzoic anhydride (159 mg, 0.70 mmol); stirring for
40 min; preparative thin layer chromatography (hexane/EtOAc, 4:1);
product 9a (66.0 mg, 76%) was obtained as a white solid. 1H NMR
(400 MHz, CDCl3) δ: 8.26 (3H, m), 8.04 (1H, d, J = 8.4 Hz), 7.83 (1H,
d, J = 8.1 Hz), 7.71 (1H, t, J = 7.4 Hz), 7.63 (1H, t, J = 7.3 Hz), 7.52
(3H, m), 7.30 (1H, d, J = 8.7 Hz, H-3); EIMS: m/z 250 [M+1]+ (2),
249 [M]+ (12), 221 (48), 145 (14), 105 (100), 77 (32); HRMS: calcd.
for C16H11NO2 249.0790, found 249.07691.
4.2.3.1. 1-Benzylquinolin-2(1H)-one
(8a). From
5
(61.1
mg,
0.41 mmol), anhydrous DMF (1 mL), NaH 40% (22 mg, 0.92 mmol)
and (bromomethyl)benzene (0.83 mmol, 98 µL); stirring for 2 h;
column chromatography (hexane/EtOAc; 4:1 to 7:3); product 8a
(77 mg, 78%) was obtained as a colorless oil. 1H NMR (400 MHz,
(CD3)2CO) δ: 7.90 (1H, d, J = 9.5 Hz, H-4), 7.68 (1H, d, J = 7.6 Hz),
7.46 (1H, dd, J = 7.4, 8.2 Hz), 7.38 (1H, d, J = 8.5 Hz), 7.31–7.26 (4H,
m), 7.23–7.17 (2H, m), 6.70 (1H, d, J = 9.5 Hz, H-3), 5.58 (2H, s, H-1′);
13C NMR (100 MHz, (CD3)2CO) δ: 162.5 (s, C-2), 140.5 (s, C-8a), 140.4
(d), 138.1 (s), 131.4 (d), 129.8 (d), 129.5 (d, 2 × C), 127.8 (d), 127.5
(d, 2 × C), 122.8 (d), 122.2 (d), 121.7 (s), 115.9 (d), 45.8 (t, C-1′);
EIMS: m/z 236 [M+1]+ (22), 235 [M]+, 100), 234 (43), 129 (44), 91
(57); HRMS: calcd. for C16H13NO 235.0997, found 235.0996.
4.2.3.7. 1-(4-Methoxybenzoyl)quinolin-2(1H)-one
(9b). From
7
(50.0 mg, 0.34 mmol), anhydrous DMF (1.7 mL), 40% NaH (41.0 mg,
1.72 mmol) and 4-methoxybenzoyl chloride (118 mg, 0.70 mmol);
stirring for 1 h 30 min; preparative thin layer chromatography (hexane/
EtOAc, 7:3); product 9b (69.9 mg, 73%) was obtained as a white solid.
1H NMR (400 MHz, CDCl3) δ: 8.22 (3H, m), 8.03 (1H, d, J = 8.4 Hz),
7.82 (1H, d, J = 8.1 Hz), 7.70 (1H, t, J = 7.5 Hz), 7.52 (1H, t,
J = 7.4 Hz), 7.29 (1H, d, J = 8.7 Hz), 6.97 (2H, d, J = 8.6 Hz), 3.85
(3H, s); 13C NMR (100 MHz, CDCl3) δ: 164.7 (s), 164.3 (s), 156.9 (s),
146.7 (s), 139.8 (d), 132.7 (d, 2 × C), 130.2 (d), 128.6 (d), 127.6 (d),
127.2 (s), 126.5 (d), 121.3 (s), 113.9 (d, 2 × C), 55.5 (c, CH3); EIMS:
m/z 280 [M+1]+ (2), 279 [M]+ (8), 152 (18), 145 (13), 135 (100);
HRMS: calcd. for C17H13NO3 279.0895, found 279.0907; UV–Vis
(EtOH) λmax: 313, 265, 230, 203, 201 nm; IR (CHCl3) νmax: 3062,
2360, 1725, 1603, 1259, 1165, 846 cm−1; mp: 82–84 °C.
4.2.3.2. 1-(4-Methoxybenzyl)quinolin-2(1H)-one
(8b). From
5
(61.1 mg, 0.41 mmol), anhydrous DMF (1 mL), NaH 40% (24 mg,
1
mmol) and 1-(chloromethyl)-4-methoxybenzene (0.83 mmol,
112 µL); stirring for 4 h; column chromatography (hexane/EtOAc,
4:1); product 8b (79 mg, 72%) was obtained as a white solid. 1H NMR
(400 MHz, CDCl3) δ: 7.72 (1H, d, J = 9.4 Hz, H-4), 7.55 (1H, d,
J = 7.7 Hz), 7.43 (1H, dd, J = 7.4, 8.0 Hz), 7.30 (1H, d, J = 8.6 Hz),
7.19–7.16 (3H, m), 6.82 (2H, d, J = 8.6 Hz), 6.79 (1H, d, J = 9.6 Hz,
H-3), 5.49 (2H, s, H-1′), 3.75 (3H, OCH3); EIMS: m/z 266 [M+1]+ (8),
265 [M]+ (50), 130 (11), 121 (100), 69 (18). HRMS: calcd. for
4.2.3.8. 1-Acetylquinolin-2(1H)-one
(9c). From
7
(55.0
mg,
0.38 mmol), anhydrous DMF (2 mL), 40% NaH (45.0 mg, 1.9 mmol)
and acetic anhydride (0.76 mmol, 72.0 µL); stirring for 5 h 30 min;
column chromatography (hexane/EtOAc, 9:1, 4:1); product 9c (35 mg,
49%) was obtained as a white solid. 1H NMR (400 MHz, CDCl3) δ: 8.25
(1H, d, J = 8.7 Hz, H-4), 8.01 (1H, d, J = 8.4 Hz), 7.85 (1H, d,
J = 8.1 Hz), 7.71 (1H, t, J = 7.6 Hz), 7.56 (1H, t, J = 7.4 Hz), 7.21
(1H, d, J = 8.7 Hz, H-3), 2.40 (3H, s, CH3); EIMS: m/z 89 (7), 117 (24),
145 (100), 146 (10), 187 [M]+ (8). HRMS: calcd. for C11H9NO2
187.0633, found 187.0631
C
17H15NO2 265.1103, found 265.1132.
4.2.3.3. (2-Oxoquinolin-1(2H)-yl)acetonitrile (8c). From 5 (0.36 mmol,
51.0 mg), anhydrous DMF (1.7 mL), NaH 40% (1.41 mmol, 33.8 mg)
and bromoacetonitrile (1.584 mmol, 117.0 µL); stirring for 5 days;
column chromatography (hexane/EtOAc, 9:1, 4:1); product 8c (42 mg,
64%) was obtained as a white solid. 1H NMR (400 MHz, CDCl3) δ: 7.75
(1H, d, J = 9.6 Hz, H-4), 7.68–7.62 (2H, m), 7.37 (1H, d, J = 8.8 Hz),
7.34 (1H, t, J = 7.4 Hz), 6.72(1H, d, J = 9.5 Hz, H-3), 5.27 (2H, s, H-
2′); EIMS: m/z 89 (12), 116 (10), 129 (26), 155 (20), 184 [M]+ (100),
185 [M+1]+ (13); HRMS: calcd. for C11H8N2O 184.0637, found
184.0643.
4.2.3.9. 1-(Morfolin-4-ylcarbonyl)quinolin-2(1H)-one (9d). From
7
(50 mg, 0.35 mmol), anhydrous DMF (2 mL), 40% NaH (24.8 mg,
1.03 mmol) and morpholine-4-carbonyl chloride (1.04 mmol,
121.0 µL); stirring for 2 h; column chromatography (hexane/EtOAc,
4:1); product 9d (25 mg, 28%) was obtained as a white solid. 1H NMR
(400 MHz, CDCl3) δ: 8.23 (1H, d, J = 8.7 Hz, H-4), 8.01 (1H, d,
J = 8.4 Hz), 7.84 (1H, d, J = 8.1 Hz), 7.72 (1H, t, J = 7.6 Hz), 7.54
(1H, t, J = 7.6 Hz), 7.25 (1H, d, J = 7.5 Hz), 3.78 (6H, br s), 3.62 (2H,
br s). 13C NMR (100 MHz, CDCl3) δ: 156.8 (s, C-2), 152.9 (s, C-1′),
146.6 (s), 139.9 (d), 130.3 (d), 128.6 (d), 127.6 (d), 127.1 (s), 126.5
(d), 115.8 (d), 66.7 (t), 66.6 (t), 45.2 (t), 44.2 (t); EIMS: m/z 258 [M]+
(21), 146 (18), 145 (100), 114 (34), 70 (36); HRMS: calcd. for
4.2.3.4. Ethyl 2-(2-oxoquinolin-1(2H)-yl)acetate (8d). From 5 (51.0 mg,
0.35 mmol), anhydrous DMF (1.7 mL), NaH 40% (34.0 mg, 1.40 mmol)
and ethyl bromoacetate (0.70 mmol, 78.0 µL); stirring for 1 h 30 min;
column chromatography (hexane/EtOAc, 9:1, 4:1); product 8d
(67.4 mg, 83%) was obtained as a white solid. 1H NMR (400 MHz,
CDCl3) δ: 7.71 (1H, d, J = 9.5 Hz, H-4), 7.57 (1H, d, J = 7.8 Hz), 7.53
(1H, dd, J = 7.7, 8.1 Hz), 7.23 (1H, t, J = 7.5 Hz), 7.10 (1H, d,
J = 8.5 Hz), 6.72 (1H, d, J = 9.5 Hz, H-3), 5.09 (2H, s, H-2′) 4.23 (2H,
c, J = 7,1 Hz, H-1″), 1.25 (3H, t, J = 7,1 Hz, CH3); EIMS: m/z 232
[M]+ (14), 231 (M+, 78), 185 (73), 158 (100), 130 (27), 129 (20), 128
C
14H14N2O3 258.1004, found 258.1004; UV–Vis (EtOH) λmax: 204,
230, 300, 313 nm; IR (CHCl3) νmax: 3587, 3064, 1719, 1196, cm−1; mp:
104–106 °C.
6